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Experimental and mathematical studies in immunology have revealed that the dynamics of the programmed T cell response to vigorous infection can be conveniently modelled using a sigmoidal or a discontinuous immune response function. This paper hypothesizes strong synergies between this existing work and the dynamical behaviour of engineering systems with a variable structure control (VSC) law. These findings motivate the interpretation of the immune system as a variable structure control system. It is shown that dynamical properties as well as conditions to analytically assess the transition from health to disease can be developed for the specific T cell response from the theory of variable structure control. In particular, it is shown that the robustness properties of the specific T cell response as observed in experiments can be explained analytically using a VSC perspective. Further, the predictive capacity of the VSC framework to determine the T cell help required to overcome chronic Lymphocytic Choriomeningitis Virus (LCMV) infection is demonstrated. The findings demonstrate that studying the immune system using variable structure control theory provides a new framework for evaluating immunological dynamics and experimental observations. A modelling and simulation tool results with predictive capacity to determine how to modify the immune response to achieve healthy outcomes which may have application in drug development and vaccine design. [ABSTRACT FROM AUTHOR]

Crohn’s Disease (CD) results from inappropriate response toward commensal flora. Earlier studies described CD as a Th1 mediated disease. Current models view both phenotypes as a continuum of various permutations between Th1, Th2 and Th17 pathways compounded by a range of Treg disfunctions. In the present paper, we develop a mathematical model, by a system of differential equations, which describe the dynamic relations among these T cells and their cytokines. The model identities four groups of CD patients according to up/down regulation of Th1 and Th2. The model simulations show that immunosuppression by TNF-α blockage benefits the group with Th1High/Th2Low while, by contrast, the group with Th1Low/Th2High will benefit from immune activation. [ABSTRACT FROM AUTHOR]

T cell response is crucial to the pathogenesis and progression of rheumatoid arthritis (RA). IL-7/IL-7R axis has significant effect on CD4 + T cell response, including proliferation, differentiation, survival and migration. However, whether blockade of IL-7/IL-7R axis signaling can relieve RA and what is the potential treatment mechanisms are still remaining unclear. In this paper, we established collagen-induced arthritis (CIA) model and observed the effect of IL-7Rα antibody in the treatment of CIA mice. It is demonstrated that IL-7Rα antibody significantly alleviated clinical symptoms of CIA mice, accompanied with reduced CD4 + T cell number in both spleen and joints. Decreased CII-specific CD4 + T cell proliferation and reduced mRNA expression of inflammatory cytokines in IL-7Rα antibody-treated mice were observed. Subsequently, IL-7Rα antibody treatment in vivo downregulated the percentages of Th1 and Th17 cells and the mRNA expression of T-bet and RORγt gene. Moreover, it was found that IL-7 promoted Th1 cell differentiation in vitro, while having no effect on Th17 cell differentiation. In addition, administration of IL-7Rα antibody reduced the mRNA expression of chemokine receptors (CCR7, CXCR3, CXCR6 and XCR1) on CD4 + T cells and chemokine CXCL2 in joints. The results suggested that IL-7Rα antibody treated CIA mice via the inhibition of CII-specific CD4 + T cell proliferation, the reduction of Th1 cell differentiation and the restrain of CD4 + T cell migration to joint lesion site. This investigation indicates that IL-7Rα is a potential therapeutic target for RA. [ABSTRACT FROM AUTHOR]

Inflammation induced by toxins, micro-organisms, or autoimmunity may result in pathogenic fibrosis, leading to long-term tissue dysfunction, morbidity, and mortality. Immune cells play a role in both induction and resolution of fibrosis. γδ T cells are an important group of unconventional T cells characterized by their expression of non-major histocompatibility complex restricted clonotypic T cell receptors for non-peptide antigens. Accumulating evidence suggests that subsets of γδ T cells in experimentally induced fibrosis following bleomycin treatment, or infection with Bacillus subtilis, play proinflammatory roles that instigate fibrosis, whereas the same cells may also play a role in resolving fibrosis. These processes appear to be linked at least in part to the cytokines produced by the cells at various stages, with interleukin (IL)-17 playing a central role in the inflammatory phase driving fibrosis, but later secretion of IL-22, interferon γ, and CXCL10 preventing pathologic fibrosis. Moreover, γδ T cells appear to be involved, in an antigen-driven manner, in the prototypic human fibrotic disease, systemic sclerosis (SSc). In this paper we review in brief the scientific publications that have implicated γδ T cells in fibrotic diseases and their pro- and anti-fibrotic effects. [ABSTRACT FROM AUTHOR]

This paper distinguishes a rare subset of myeloid dendritic-like cells found in mouse spleen from conventional (c) dendritic cells (DC) in terms of phenotype, function and gene expression. These cells are tentatively named “L-DC” since they resemble dendritic-like cells produced in longterm cultures of spleen. L-DC can be distinguished on the basis of their unique phenotype as CD11bhiCD11cloMHCII-CD43+Ly6C-Ly6G-Siglec-F- cells. They demonstrate similar ability as cDC to uptake and retain complex antigens like mannan via mannose receptors, but much lower ability to endocytose and retain soluble antigen. While L-DC differ from cDC by their inability to activate CD4+ T cells, they are capable of antigen cross-presentation for activation of CD8+ T cells, although less effectively so than the cDC subsets. In terms of gene expression, CD8- cDC and CD8+ cDC are quite distinct from L-DC. CD8+ cDC are distinguishable from the other two subsets by expression of CD24a, Clec9a, Xcr1 and Tlr11, while CD8- cDC are distinguished by expression of Ccnd1 and H-2Eb2. L-DC are distinct from the two cDC subsets through upregulated expression of Clec4a3, Emr4, Itgam, Csf1r and CD300ld. The L-DC gene profile is quite distinct from that of cDC, confirming a myeloid cell type with distinct antigen presenting properties. [ABSTRACT FROM AUTHOR]

The immune repertoire (IR) refers to the sum of B cells and T cells with functional diversity in the circulatory system of one individual at any given time. Immune cells, which reside within microenvironments and are responsible for protecting the human body, include T cells, B cells, macrophages, and dendritic cells. These dedicated immune cells have a characteristic structure and function. T and B cells are the main lymphocytes and are responsible for cellular immunity and humoral immunity, respectively. The T cell receptor (TCR) and B cell receptor (BCR) are composed of multiple peptide chains with antigen specificity. The amino acid composition and sequence order are more diverse in the complementarity-determining regions (including CDR1, CDR2 and CDR3) of each peptide chain, allowing a vast library of TCRs and BCRs. IR research is becoming increasingly focused on the study of CDR3 diversity. Deep profiling of CDR3s using high-throughput sequencing is a powerful approach for elucidating the composition and distribution of the CDR3s in a given sample, with in-depth information at the sequence level. Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. To identify novel biomarkers for diagnosis and drug targets for therapeutic interventions, several groups attempted to describe immune repertoire characteristics of the liver in the physiological environment or/and pathological conditions. This paper reviews the recent progress in IR research on human diseases, including hepatocellular carcinoma, attempting to depict the relationships between hepatocellular carcinogenesis and the IR, and discusses the possibility of IR as a potential biomarker and therapeutic for hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Angiopoietin-1/Tie2 (ANG1/Tie2) signaling is well documented as regulating angiogenesis and vessel maturation. This pathway is complicated by involvement of the orphan receptor Tie1, which has been implicated as both a positive and negative regulator of ANG1/Tie2 signaling, and ANG2, which can serve as both a Tie2 agonist and antagonist, depending on the context. Two papers in this issue of the JCI provide new insight into this complicated pathway. Korhonen et al. reveal that Tie1 acts to modulate the effects of ANG1 and ANG2 on Tie2 in vitro and in vivo. Kim et al. demonstrate that ANG2 acts as a Tie2 agonist in non-pathological conditions, whereas in the setting of inflammation, ANG2 functions as a Tie2 antagonist and promotes vascular dysfunction. Both studies indicate that inflammation promotes cleavage of the ectodomain of Tie1 and that this cleavage event corresponds with the switch of ANG2 from a Tie2 agonist to an antagonist. The results of these studies lay the groundwork for future strategies to therapeutically exploit this pathway in diseases characterized by adverse vascular remodeling and increased permeability. [ABSTRACT FROM AUTHOR]

In this paper, we construct an HIV infection model which includes latent infection, logistic growth for healthy CD4 T-cells, and antiretroviral therapy. We obtain the global asymptotic stability of the uninfected equilibrium by constructing a Lyapunov function, and we give a sufficient condition for the local asymptotic stability of the infected equilibrium. We also use the latin hypercube sampling technique to identify the key parameters in determining the stability of the infected equilibrium. By numerical simulations, we observe that the model without logistic growth would underestimate the number of infectious virions, while the model without latent infection would overestimate the number of infectious virions. [ABSTRACT FROM AUTHOR]

The ongoing epidemics of metabolic diseases and increase in the older population have increased the incidences of neurodegenerative diseases. Evidence from murine and cell line models has implicated calcineurin-nuclear factor of activated T-lymphocytes (NFAT) signaling pathway, a Ca2+/calmodulin-dependent major proinflammatory pathway, in the pathogenesis of these diseases. Neurotoxins such as amyloid-β, tau protein, and α-synuclein trigger abnormal calcineurin/NFAT signaling activities. Additionally increased activities of endogenous regulators of calcineurin like plasma membrane Ca2+-ATPase (PMCA) and regulator of calcineurin 1 (RCAN1) also cause neuronal and glial loss and related functional alterations, in neurodegenerative diseases, psychotic disorders, epilepsy, and traumatic brain and spinal cord injuries. Treatment with calcineurin/NFAT inhibitors induces some degree of neuroprotection and decreased reactive gliosis in the central and peripheral nervous system. In this paper, we summarize and discuss the current understanding of the roles of calcineurin/NFAT signaling in physiology and pathologies of the adult and developing nervous system, with an emphasis on recent reports and cutting-edge findings. Calcineurin/NFAT signaling is known for its critical roles in the developing and adult nervous system. Its role in physiological and pathological processes is still controversial. However, available data suggest that its beneficial and detrimental effects are context-dependent. In view of recent reports calcineurin/NFAT signaling is likely to serve as a potential therapeutic target for neurodegenerative diseases and conditions. This review further highlights the need to characterize better all factors determining the outcome of calcineurin/NFAT signaling in diseases and the downstream targets mediating the beneficial and detrimental effects. [ABSTRACT FROM AUTHOR]

Myeloid-derived suppressor cells are a heterogeneous group of immature myeloid cells with immunoregulatory function. When activated and expanded, these cells can suppress T cell functions via cell-to cell interactions as well as soluble mediators. Recent studies investigated the involvement of MDSC in autoimmune diseases. Some papers have described beneficial effect of MDSC during the course of autoimmune diseases, and suggest a potential role as a treatment option, while others failed to detect these effects. Their contributions to autoimmune diseases are not fully understood, and many questions and some controversies remain as to the expansion, activation, and inhibitory functions of MDSC. This review aims to summarize current knowledge of MDSC in autoimmune disorders. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the dynamical behavior of a nonlinear model for viral infection with Cytotoxic T Lymphocyte (CTL) immune response. The model is a generalization of several models presented in the literature by considering more general functions for the: (i) intrinsic growth rate of uninfected cells; (ii) incidence rate of infection; (iii) natural death rate of infected cells; (iv) rate at which the infected cells are killed by CTL cells; (v) production and removal rates of viruses; (vi) activation and natural death rates of CTLs. We derive two threshold parameters R0 (the basic infection reproduction number) and R1 (the CTL immune response activation number) and establish a set of conditions on the general functions which are sufficient to determine the global dynamics of the model. By using suitable Lyapunov functions and LaSalle's invariance principle, we prove the global asymptotic stability of all equilibria of the model. [ABSTRACT FROM AUTHOR]

The koala ( Phascolarctos cinereus ) is an arboreal herbivorous marsupial that is an Australian icon. Koalas in many parts of Australia are under multiple threats including habitat destruction, dog attacks, vehicular accidents, and infectious diseases such as Chlamydia spp. and the koala retrovirus (KoRV), which may contribute to the incidence of lymphoma and leukaemia in this species. Due to a lack of koala-specific immune reagents and assays there is currently no way to adequately analyse the immune response in healthy, diseased or vaccinated animals. This paper reports the production and characterisation of the first anti-koala CD4 monoclonal antibody (mAb). The koala CD4 gene was identified and used to develop recombinant proteins for mAb production. Fluorochrome-conjugated anti-CD4 mAb was used to measure the levels of CD4 + lymphocytes collected from koala spleens (41.1%, range 20–45.1%) lymph nodes (36.3%, range 19–55.9%) and peripheral blood (23.8%, range 17.3–35%) by flow cytometry. Biotin-conjugated anti-CD4 mAb was used for western blot to determine an approximate size of 52 kDa for the koala CD4 molecule and used in immunohistochemistry to identify CD4 + cells in the paracortical region and germinal centres of spleen and lymph nodes. Using the anti-CD4 mab we showed that CD4 cells from vaccinated, but not control, koalas proliferated following in vitro stimulation with UV-inactivated Chlamydia pecorum and recombinant chlamydial antigens. Since CD4 + T cells have been shown to play a pivotal role in clearing chlamydial infection in both human and mouse infections, using this novel antibody will help determine the role CD4 + T cells play in protection against chlamydial infection in koalas and also enhance our knowledge of how KoRV affects the koala immune system. [ABSTRACT FROM AUTHOR]

Emerging evidence reveals the controversial role of B cells in antitumor immunity, but the underlying mechanisms have to be explored. Three latest articles published in the issue 521 of Nature in 2015 reconfirmed the puzzling topic and put forward some explanations of how B cells regulate antitumor T-cell responses both positively and negatively. This paper attempts to demonstrate that different B-cell subpopulations have distinct immunological properties and that they are involved in either antitumor responses or immunosuppression. Recent studies supporting the positive and negative roles of B cells in tumor development were summarized comprehensively. Several specific B-cell subpopulations, such as IgG(+), IgA(+), IL-10(+), and regulatory B cells, were described in detail. The mechanisms underlying the controversial B-cell effects were mainly attributed to different B-cell subpopulations, different B-cell-derived cytokines, direct B cell-T cell interaction, different cancer categories, and different malignant stages, and the immunological interaction between B cells and T cells is mediated by dendritic cells. Promising B-cell-based antitumor strategies were proposed and novel B-cell regulators were summarized to present interesting therapeutic targets. Future investigations are needed to make sure that B-cell-based pharmacological strategies benefit cancer immunotherapy substantially. [ABSTRACT FROM AUTHOR]

• We systematically and in detail summarize the classification and biological characteristics of DC, as well as its development process. We focus on and deeply understand the role of DC in regulating the pathogenesis of different allergic diseases. • We demonstrate for the frist time the role of dendritic cells in various allergic diseases including AR, AA, AD, and FA. • Based on inflammatory response and immune regulation, a better understanding of the role of DC in immunomodulation and Th2 immune response can guide the development of new therapeutic targets for various allergic diseases and provide new ideas for the treatment of patients with allergic diseases. Allergic diseases are important diseases that affect many patients worldwide. Over the past few decades, the incidence of allergic diseases has increased significantly due to social development and increased environmental degradation, which has placed a huge economic burden on public health and even led to an increase in mortality. Substantial progress has been made in the understanding of the mechanisms of allergic diseases, and past studies have shown that the occurrence and development of allergic diseases are closely related to changes in the state of the immune system. With the study and in-depth understanding of innate immune lymphocytes, researchers have gradually discovered that dendritic cells (DC) play an important role in many allergic diseases. DC are the body's main antigen-presenting cells, which ingest, process, and hand allergens, and then secrete chemokines such as chemokine ligands 17(CCL17), CCL22, and upregulate their own surface co-stimulating molecules. Then DC present the antigen peptide to the initial T cells and further differentiate them into helper T cells 2(Th2). As an important part of humoral immunity, Th2 participates in the regulation of type 2 immune response through the secretion of cytokines such as interleukin 4(IL-4), IL-5, and IL-13 and plays a leading role. However, our current research on DC is limited and its status in allergic diseases is unclear.Among them, allergic rhinitis, allergic asthma, atopic dermatitis, and food allergy are DC-mediated Th2 immune-related factor disorder-related allergic diseases, and some progress has been made in recent years in the study of the pathogenesis of these diseases. This paper outlines the common phenotypes and activation pathways of DC in different allergic diseases as well as potential research directions to improve the understanding of its immunomodulatory role in different allergic diseases and ultimately find new ways to treat these diseases. [ABSTRACT FROM AUTHOR]

Zukamu granules (ZKMG), as the preferred drug for the treatment of colds in Uygur medical theory, has been used for 1500 years. It is also widely used in China and included in the National Essential Drugs List (2018 edition). It has unique anti-inflammatory, antitussive and analgesic effects. Aiming at the research of traditional Chinese medicine (TCM) with the characteristics of overall regulation of body diseases and the immune regulation mechanism with the concept of integrity, this paper put forward the integrated application of network composite module analysis and animal experiment verification to study the immune regulation mechanism of TCM. The active components and targets of ZKMG were predicted, and network module analysis was performed to explore their potential immunomodulatory mechanisms. Then acute lung injury (ALI) mice and idiopathic pulmonary fibrosis (IPF) rats were used as pathological models to observe the effects of ZKMG on the pathological conditions of infected ALI and IPF rats, determine the contents of Th1, Th2 characteristic cytokines and immunoglobulins, and study the intervention of GATA3/STAT6 signal pathway. The results of network composite module analysis showed that ZKMG contained 173 pharmacodynamic components and 249 potential targets, and four key modules were obtained. The immunomodulatory effects of ZKMG were related to T cell receptor signaling pathway. The validation results of bioeffects that ZKMG could carry out bidirectional immune regulation on Th1/Th2 cytokines in the stage of ALI and IPF, so as to play the role of regulating immune homeostasis and organ protection. The network composite module analysis and verification method is an exploration to study the immune regulation mechanism of TCM by combining the network module prediction analysis with animal experiments, which provides a reference for subsequent research. [Display omitted] [ABSTRACT FROM AUTHOR]

The newly discovered subset of memory T cells, tissue resident memory T (TRM) cells, reside in peripheral tissues for a long time, contributing to a rapid immune response and constituting the first line of defense when pathogens invade cells. Tissue resident memory T cells have unique transcriptome characteristics, and their presence in peripheral tissues is regulated by many factors. TRM cells residing in different tissues often express different surface markers. In addition to CD8+ and CD4+ T cells, which are the best-characterized T cells, Treg cells and various innate T cells can reside in nonlymphoid tissues. Many recent studies have shown that tissue resident memory T cells play indispensable roles in tumor immunity and allergic diseases. This paper reviews the differentiation, regulation, variety and function of TRM cells and the roles they play in skin diseases, including cutaneous melanoma and psoriasis. • Tissue-resident memory T cells exhibit distinct tissue-specific and niche-specific functions in immune detection network. • Multiple factors control the development and resident of Tissue-resident memory T cell. • Tissue-resident memory T cells participate in skin inflammation and contribute tomaintaining the recurrence of skin diseases. [ABSTRACT FROM AUTHOR]

This paper presents a high-stability low-power 10 T (HSLP10T) sub-threshold SRAM cell with single-ended operations. The HSLP10T cell uses a decoupled read path, formed by a transmission gate and a dynamic inverter, thereby, resulting in read stability improvement. In addition, it employs a feedback-cutting transistor to facilitate the write operation, which increases writability. Due to single-ended operations, direct-write on complementary node, floated bitline, and use of more p-type transistors, the power consumption reduces in the proposed cell. Simulated results in the 7-nm FinFET technology indicate that at a 300 mV supply voltage, the read stability/writability of the proposed HSLP10T cell is 2.06X/1.31X as that of the conventional 6 T cell. Moreover, the dynamic/leakage power consumption is reduced by 1.82X/2.92X when compared with the conventional 6 T SRAM. The proposed HSLP10T SRAM bitcell has a layout area of 0.047 µm2, which is 1.67 × larger than the conventional 6 T SRAM. However, the highest ON-to-OFF currents ratio related to the proposed design compensates for this area overhead by connecting more number of cells to the same bitline in the columns of the SRAM array. Moreover, the minimum operation voltage is reduced by 48.28 % using proposed design compared to the conventional 6 T SRAM. [ABSTRACT FROM AUTHOR]

Psoriasis is a common inflammatory skin disease involving interactions between keratinocytes and immune cells that significantly affects the quality of life. It is characterized by hyperproliferation and abnormal differentiation of keratinocytes and excessive infiltration of immune cells in the dermis and epidermis. The immune mechanism underlying this disease has been elucidated in the past few years. Research shows that psoriasis is regulated by the complex interactions among immune cells, such as keratinocytes, dendritic cells, T lymphocytes, neutrophils, macrophages, natural killer cells, mast cells, and other immune cells. An increasing number of signaling pathways have been found to be involved in the pathogenesis of psoriasis, which has prompted the search for new treatment targets. In the past decades, studies on the pathogenesis of psoriasis have focused on the development of targeted and highly effective therapies. In this review, we have discussed the relationship between various types of immune cells and psoriasis and summarized the major signaling pathways involved in the pathogenesis of psoriasis, including the PI3K/AKT/mTOR, JAK-STAT, JNK, and WNT pathways. In addition, we have discussed the results of the latest omics research on psoriasis and the epigenetics of the disease, which provide insights regarding its pathogenesis and therapeutic prospects; we have also summarized its treatment strategies and observations of clinical trials. In this paper, the various aspects of psoriasis are described in detail, and the limitations of the current treatment methods are emphasized. It is necessary to improve and innovate treatment methods from the molecular level of pathogenesis, and further provide new ideas for the treatment and research of psoriasis. • The relationship between various immune cells and psoriasis is discussed. • Major signaling pathways involved in the pathogenesis of psoriasis are summarized. • Results of the latest omics research on psoriasis are discussed. • Treatment strategies and clinical trial observations for psoriasis are summarized. [ABSTRACT FROM AUTHOR]

• We systematically and in detail summarize the classification and biological characteristics of DC, as well as its development process. We focus on and deeply understand the role of DC in regulating the pathogenesis of different allergic diseases. • We demonstrate for the frist time the role of dendritic cells in various allergic diseases including AR, AA, AD, and FA. • Based on inflammatory response and immune regulation, a better understanding of the role of DC in immunomodulation and Th2 immune response can guide the development of new therapeutic targets for various allergic diseases and provide new ideas for the treatment of patients with allergic diseases. Allergic diseases are important diseases that affect many patients worldwide. Over the past few decades, the incidence of allergic diseases has increased significantly due to social development and increased environmental degradation, which has placed a huge economic burden on public health and even led to an increase in mortality. Substantial progress has been made in the understanding of the mechanisms of allergic diseases, and past studies have shown that the occurrence and development of allergic diseases are closely related to changes in the state of the immune system. With the study and in-depth understanding of innate immune lymphocytes, researchers have gradually discovered that dendritic cells (DC) play an important role in many allergic diseases. DC are the body's main antigen-presenting cells, which ingest, process, and hand allergens, and then secrete chemokines such as chemokine ligands 17(CCL17), CCL22, and upregulate their own surface co-stimulating molecules. Then DC present the antigen peptide to the initial T cells and further differentiate them into helper T cells 2(Th2). As an important part of humoral immunity, Th2 participates in the regulation of type 2 immune response through the secretion of cytokines such as interleukin 4(IL-4), IL-5, and IL-13 and plays a leading role. However, our current research on DC is limited and its status in allergic diseases is unclear.Among them, allergic rhinitis, allergic asthma, atopic dermatitis, and food allergy are DC-mediated Th2 immune-related factor disorder-related allergic diseases, and some progress has been made in recent years in the study of the pathogenesis of these diseases. This paper outlines the common phenotypes and activation pathways of DC in different allergic diseases as well as potential research directions to improve the understanding of its immunomodulatory role in different allergic diseases and ultimately find new ways to treat these diseases. [ABSTRACT FROM AUTHOR]

As genetically engineered cells, chimeric antigen receptor (CAR)-T cells express specific receptors on their surface to target and eliminate malignant cells. CAR proteins are equipped with elements that enhance the activity and survival of T cells. Once injected, CAR-T cells act as a "living drug" against tumor cells in the body. Up to now, CAR-T cell therapy has been demonstrated as a robust adoptive cell transfer (ACT) immunotherapeutic modality for eliminating tumor cells in refractory hematological malignancies. CAR-T cell therapy modality involves several steps, including the collecting of the blood from patients, the isolation of peripheral blood mononuclear cells (PBMCs), the enrichment of CD4+/CD8+ T cell, the genetic reprogramming, the expansion of modified T cells, and the injection of genetically engineered T cells. The production of CAR-T cells is a multi-step procedure, which needs precise and safety management systems, including good manufacturing practice (GMP), and in-line quality control and assurance. The current study describes the structure of CARs and concentrates on the next generations of CARs that are engaged in enhancing the anti-tumor responses and safety of the engineered T cells. This paper also highlights the important concerns in quality control and nonclinical research of CAR-T cells, as well as general insights into the manufacture, reprogramming, and application of CAR-T cells based on new and enhanced techniques for treating hematological malignancies. Besides, the application of the CRISPR-Cas9 genome editing technology and nanocarrier-based delivery systems containing CAR coding sequences to overcome the limitations of CAR-T cell therapy has also been explained. [Display omitted] [ABSTRACT FROM AUTHOR]

• Two numerical methods are developed for solving the fractional-order HIV-1 infection model of CD4 + T-cells. • Two method (Bessel matrix method and Bessel quasilinearization method) are based on the novel Bessel polynomials. • Error and convergence analysis are studied. • Numerical applications and comparisons show that methods are effective. • In the comparison of the two methods used, the Bessel-QLM method gives better results. In this paper, two numerical methods based on the novel Bessel polynomials are developed to solve the fractional-order HIV-1 infection model of CD 4 + T-cells considering the impact of antiviral drug treatment. In first of these methods, by using the Bessel polynomial and collocation points, we transform the HIV problem into a system of nonlinear algebraic equations. And this method, which is the method of direct solution is called as Bessel matrix method. The second method, which is called the Bessel-QLM method converts firstly HIV problem to a sequence of linear equations by using the technique of quasilinearization and then the reduced problem is solved by the direct Bessel matrix method. Error and convergence analysis are studied for the Bessel method. Finally, the applications are made on the numerical examples and also the numerical results are compared with the results of other available techniques. It is observed from applications that the presented results are better than the results of other existing methods and also the Bessel-QLM method is more efficient than the direct Bessel method. [ABSTRACT FROM AUTHOR]

Presents an abstract of the paper entitled `Potassium Current Suppression by CD40 Antibody in Human B Lymphocytes,' by John D. Gallagher, Randolph J. Noelle, and Frances V. McCann presented at the 1994 meeting of the Society of General Physiologists at the Marine Biological Laboratory in Woods Hole, Massachusetts. Impact of T helper cells; Effects of CD40 antibody on potassium current.

Presents an abstract of the paper entitled `Intracellular Ca2+ Thresholds for Interleukin 2 Gene Expression in Single T Lymphocytes,' by Paul A. Negulescu, Nilabh Shastri and Michael D. Cahalan presented at the 1993 meeting of the Society of General Physiologists held at the Marine Biological Laboratory in Woods Hole, Massachusetts. Role of calcium ion in the regulation of interleukin 2.

In this paper, immune systems and its relationships with multi-robot shepherding problems are discussed. The proposed algorithm is based on immune network theories that have many similarities with the multi-robot systems domain. The underlying immune-inspired cooperative mechanism of the algorithm is simulated and evaluated. The paper also describes a refinement of the memory-based immune network that enhances a robot's action-selection process. A refined model, which is based on the Immune Network T-cell-regulated - with Memory (INT-M) model, is applied to the dog-sheep scenario. The refinements involves the low-level behaviors of the robot dogs, namely shepherds' formation and shepherds' approach. These behaviors would make the shepherds form a line behind the group of sheep and also obey a safety zone of each flock, thus achieving better control of the flock and minimize flock separation occurrences. Simulation experiments are conducted on the Player/Stage robotics platform. [ABSTRACT FROM AUTHOR]

The major focus of this paper is to describe and evaluate current information on the role of natural killer cells (NK cells) in the pathogenesis of blistering diseases. Until now, only pemphigus vulgaris (PV) has been studied. One co-culture study demonstrated that CD4++ T cells from the peripheral blood or perilesional skin of patients with active disease proliferate and secrete cytokines in the presence of major histocompatibility class II-expressing NK cells loaded with antigenic desmoglein self-peptides. Another study showed that NK cells can contribute to a T helper type 2-biased immune response through impaired interleukins (IL)-12 signaling and upregulation of IL, IL-10 and IL-5. Although significant data on other blistering diseases are unavailable at present, some studies implicate NK cells in disease progression. For instance, information on the role of NK cells in psoriasis and their production of tumor necrosis factor-α (TNF-α) will be provided since several TNF-α-inhibitors are used in its treatment. Studies on alopecia areata are also included in this paper because NK cells seem to play a key role in its pathogenesis. This review highlights the potential importance of NK cells and NKT cells as members of the large repertoire of cells and soluble mediators that play a critical role in pathogenesis of blistering diseases and other autoimmune diseases involving the skin. Therefore, the authors advocate a greater focus and interest on the study of the interaction of NK cells and the skin. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, and CD4+ T cells formthe core immunopathogenic cascade leading to chronic inflammation. Traditionally, Th1 cells (interferon-γ-producing CD4+ T cells) driven by interleukin 12 (IL12) were considered to be the encephalitogenic T cells in MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Currently, Th17 cells (Il17-producing CD4+ T cells) are considered to play a fundamental role in the immunopathogenesis of EAE. This paper highlights the growing evidence that Th17 cells play the core role in the complex adaptive immunity of EAE/MS and discusses the roles of the associated immune cells and cytokines. These constitute the modern immunological basis for the development of novel clinical and preclinical immunomodulatory therapies for MS discussed in this paper. [ABSTRACT FROM AUTHOR]

Background: Various computational models have been of interest due to their use in the modelling of gene regulatory networks (GRNs). As a logical model, probabilistic Boolean networks (PBNs) consider molecular and genetic noise, so the study of PBNs provides significant insights into the understanding of the dynamics of GRNs. This will ultimately lead to advances in developing therapeutic methods that intervene in the process of disease development and progression. The applications of PBNs, however, are hindered by the complexities involved in the computation of the state transition matrix and the steady-state distribution of a PBN. For a PBN with n genes and N Boolean networks, the complexity to compute the state transition matrix is O(nN22n) or O(nN2n) for a sparse matrix. Results: This paper presents a novel implementation of PBNs based on the notions of stochastic logic and stochastic computation. This stochastic implementation of a PBN is referred to as a stochastic Boolean network (SBN). An SBN provides an accurate and efficient simulation of a PBN without and with random gene perturbation. The state transition matrix is computed in an SBN with a complexity of O(nL2n), where L is a factor related to the stochastic sequence length. Since the minimum sequence length required for obtaining an evaluation accuracy approximately increases in a polynomial order with the number of genes, n, and the number of Boolean networks, N, usually increases exponentially with n, L is typically smaller than N, especially in a network with a large number of genes. Hence, the computational efficiency of an SBN is primarily limited by the number of genes, but not directly by the total possible number of Boolean networks. Furthermore, a time-frame expanded SBN enables an efficient analysis of the steady-state distribution of a PBN. These findings are supported by the simulation results of a simplified p53 network, several randomly generated networks and a network inferred from a T cell immune response dataset. An SBN can also implement the function of an asynchronous PBN and is potentially useful in a hybrid approach in combination with a continuous or single-molecule level stochastic model. Conclusions: Stochastic Boolean networks (SBNs) are proposed as an efficient approach to modelling gene regulatory networks (GRNs). The SBN approach is able to recover biologically-proven regulatory behaviours, such as the oscillatory dynamics of the p53-Mdm2 network and the dynamic attractors in a T cell immune response network. The proposed approach can further predict the network dynamics when the genes are under perturbation, thus providing biologically meaningful insights for a better understanding of the dynamics of GRNs. The algorithms and methods described in this paper have been implemented in Matlab packages, which are attached as Additional files. [ABSTRACT FROM AUTHOR]

MicroRNAs govern immune responses to infectious agents, allergens, and autoantigens and function by posttranscriptional repression of their target genes. In this paper, we have addressed the role of microRNA-155 (miR-155) in the control of Helicobacter pylori infection of the gastrointestinal tract and the development of H. pylori-induced chronic gastritis and associated gastric preneoplastic pathology. We show that miR-155 is upregulated in the gastric mucosa of experimentally infected mice and that miR-155-/- mice fail to control H. pylori infection as a result of impaired pathogen-specific Th1 and Th17 responses. miR-155-/- mice are also less well protected against challenge infection after H. pylori-specific vaccination than their wild-type (wt) counterparts. As a consequence of their impaired T cell responses to H. pylori, miR-155-/- mice develop less severe infection-induced immunopathology manifesting as chronic atrophic gastritis, epithelial hyperplasia, and intestinal metaplasia. T cells from miR-155-/- mice that are activated by CD3/CD28 cross-linking expand less and produce less IFN-γ and IL-17 than wt T cells. Finally, we show in this paper using adoptive transfers that the phenotypes of miR-155-/- mice are likely due to T cell-intrinsic defects. In contrast to wt T cells, miR-155-/- T cells from infected donors do not control H. pylori infections in T cell-deficient recipients, do not differentiate into Th1 or Th17 cells, and do not cause immunopathology. In addition, naive miR-155-/- T cells fail to induce chronic Th17-driven colitis in an adoptive transfer model. In conclusion, miR-155 expression is required for the Th17/Th1 differentiation that underlies immunity to H. pylori infection on the one hand and infection-associated immunopathology on the other. [ABSTRACT FROM AUTHOR]

Introduction. Paraneoplastic neurological syndromes (PNS) refer to a diverse group of nervous system disorders associated with tumors. They are not directly caused by a tumor’s immediate expansion, compression resulting from it, infiltration or anticancer treatment. Their pathomechanism involves damage to the nervous system as a result of the organism’s immune response directed against cancer antigens, and also against antigens occurring physiologically in the nervous system. Onconeural antibodies and cytotoxic T lymphocytes are responsible for the immune response. These conditions are quite rare - fewer than 1 person out of 100 patients suffering from cancer develops PNS. They often precede a direct manifestation of cancer. The best known PNS conditions include: Lambert-Eaton myasthenic syndrome, paraneoplastic cerebellar degeneration, and polyneuropathies. PNS was identified for the first time in 1949. Nowadays, the criteria established in 2004 by Graus et al. have been followed in diagnostics. These define the conditions for arriving at a possible and definite diagnosis based on the presence of a characteristic neurological syndrome, the presence of onconeural antibodies, and detecting neoplasm before or after the manifestation of neurological symptoms. Diagnosis is difficult due to the lack of laboratory markers (onconeural antibodies are present in serum only in 50-60% of cases) or direct cancer symptoms in the first phase of the disease. Aim. This paper aimed at recounting the existence of a very rare neurological syndrome, limbic encephalitis, which can develop in the course of a neoplastic disease. Awareness of PNS and detecting neoplasm beforeits direct clinical manifestation can contribute to a better prognosis for patients.Materials and methods. This paper is based on a case analysis concerning a patient manifesting symptoms of the limbic system involvement. The medical history has been interpreted, additional examination results have been analyzed, and the developing clinical manifestations have been investigated. Case study. The presented patient is a 45-year old man in whose case limbic encephalitis exceeded detecting abdominal cancer by a year. Diagnostic difficulties were caused by a synchronous pituitary microadenoma and hormonal disturbances involving cortisol and prolactin, which suggested Cushing’s syndrome. The main clinical symptoms, intensifying in time during the course of the disease lasting several months included: recent memory disturbances, allopsychic disorientation, depression, and periodical aggression. Results and discussion. Conducted serum tests to screen for onconeural antibodies did not confirm their presence. However, a magnetic resonance imaginig (MRI) scan revealed bilateral hippocampal damage. On the basis of a typical clinical syndrome, and cancer identified after a year following the occurrence of the symptoms, a definite, according to Graus’ criterion, diagnosis of PNS was established. Conclusions. Awareness and knowledge of PNS contributes to an early diagnosis and detection of cancer. This creates an opportunity to introduce adequate treatment and improves the prognosis for the patient. [ABSTRACT FROM AUTHOR]

Abstract: Three years ago, the Journal of Autoimmunity and Autoimmunity Reviews launched a series of special issues devoted to the contributions of outstanding scholars in autoimmunology. The special issues are devoted not only to recognize achievements, but also to include a series of dedicated papers that reflect the scholar’s work, but also are cutting-edge research and reviews in immunology. This special issue is devoted to Haralampos M. Moutsopoulos of the National University of Athens. His contributions to patient care, teaching, and original research are legion. The papers that are included reflect not only a wide range of scholarship in autoimmunology, but importantly are written by his colleagues and friends, and by former students. They encompass original scholarship in Sjögren’s syndrome, but also in a number of effector pathways in both adult and pediatric autoimmunology. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Upregulation of cathepsin S in psoriatic keratinocytes. Experimental Dermatology 2010; 19: e80-e88. Abstract: Cathepsin S (CATS) is a cysteine protease, well known for its role in MHC class II-mediated antigen presentation and extracellular matrix degradation. Disturbance of the expression or metabolism of this protease is a concomitant feature of several diseases. Given this importance we studied the localization and regulation of CATS expression in normal and pathological human/mouse skin. In normal human skin CATS-immunostaining is mainly present in the dermis and is localized in macrophages, Langerhans, T- and endothelial cells, but absent in keratinocytes. In all analyzed pathological skin biopsies, i.e. atopic dermatitis, actinic keratosis and psoriasis, CATS staining is strongly increased in the dermis. But only in psoriasis, CATS-immunostaining is also detectable in keratinocytes. We show that cocultivation with T-cells as well as treatment with cytokines can trigger expression and secretion of CATS, which is involved in MHC II processing in keratinocytes. Our data provide first evidence that CATS expression (i) is selectively induced in psoriatic keratinocytes, (ii) is triggered by T-cells and (iii) might be involved in keratinocytic MHC class II expression, the processing of the MHC class II-associated invariant chain and remodeling of the extracellular matrix. This paper expands our knowledge on the important role of keratinocytes in dermatological disease. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we introduce fractional-order into a model of HIV infection of CD4+ T-cells. We show that the model established in this paper possesses non-negative solutions, as desired in any population dynamics. We also carry out a detailed analysis on the stability of equilibrium. Numerical simulations are presented to illustrate the results. [Copyright &y& Elsevier]

First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Chiara Cassioli is first author on 'The Bardet-Biedl syndrome complex component BBS1 controls T cell polarity during immune synapse assembly', published in JCS. Chiara is a postdoc in the lab of Cosima T. Baldari at the University of Siena, Italy, investigating regulation of immune synapse assembly in the non-ciliated T cells by components of the ciliary machinery. [ABSTRACT FROM AUTHOR]

In the early 1970s a spate of papers by research groups around the world provided evidence for a negative regulatory role of thymus-derived lymphocytes (T cells). In 1971, Gershon and Kondo published a seminal paper in Immunology entitled ‘Infectious Immunological Tolerance’ 1 indicating that such negative regulation could be a dominant effect that prevented otherwise ‘helpful’ T cells from mediating their function. Over the next decade, suppressor T cells, as these negative regulatory cells became known, were intensively investigated and a complex set of interacting cells and soluble factors were described as mediators in this process of immune regulation. In the early 1980s, however, biochemical and molecular experiments raised questions about the interpretation of the earlier studies, and within a few years, the term ‘suppressor T cell’ had all but disappeared from prominence and research on this phenomenon was held in poor esteem. While this was happening, new studies appeared suggesting that a subset of T cells played a critical role in preventing autoimmunity. These T cells, eventually dubbed ‘regulatory T cells’, have become a major focus of modern cellular immunological investigation, with a predominance that perhaps eclipses even that seen in the earlier period of suppressor T cell ascendancy. This brief review summarizes the rise and fall of ‘suppressorology’ and the possibility that Tregs are a modern rediscovery of suppressor T cells made convincing by more robust models for their study and better reagents for their identification and analysis. [ABSTRACT FROM AUTHOR]

From a historical perspective, the studies that led to the isolation and characterization of the thymosins began in earnest in the early 1960s in the laboratory of Abraham White at the Albert Einstein College of Medicine in New York. In a 1966 paper in the Proceedings of the National Academy of Sciences, U.S., we first named these thymic-derived factors “Thymosins.” By 1972, the thymosin team had moved to the University of Texas Medical Branch in Galveston (UTMB) where an extremely talented group of young scientists and students succeeded over the next 6 years in preparing and testing a highly active partially purified calf thymus preparation, termed thymosin fraction-5 (TF5), which was amenable for scale-up and suitable for clinical use. In 1974, we received the first IND for a thymic hormone preparation from the FDA to begin a phase-I study with TF5 in children with primary immunodeficiency diseases at the University of California Medical Center in San Francisco. The immunorestorative and potentially life-saving properties of TF5 in clinical medicine were first documented in a landmark paper in 1975 by Drs. Arthur Ammann and Diane Wara in the New England Journal of Medicine. TF5 consists of a family of at least 40 mostly small acidic polypeptides, with molecular weights ranging from 1000 to 15,000 Da. This article will identify the key scientists and the milestones involved in the initial studies with TF5 that have led to the chemical characterization of the thymosins and to translational studies from the lab bench to the clinic. [ABSTRACT FROM AUTHOR]

Background: Investigation of host responses to blood stages of Plasmodium spp, and the immunopathology associated with this phase of the life cycle are often performed on mice infected directly with infected red blood cells. Thus, the effects of mosquito bites and the pre-erythrocytic stages of the parasite, which would be present in natural infection, are ignored In this paper, Plasmodium chabaudi chabaudi infections of mice injected directly with infected red blood cells were compared with those of mice infected by the bites of infected mosquitoes, in order to determine whether the courses of primary infection and splenic CD4 T cell responses are similar. Methods: C57Bl/6 mice were injected with red blood cells infected with P. chabaudi (ER) or infected via the bite of Anopheles stephensi mosquitoes. Parasitaemia were monitored by Giemsastained thin blood films. Total spleen cells, CD4+ T cells, and cytokine production (IFN-γ, IL-2, IL-4, IL-10) were analysed by flow cytometry. In some experiments, mice were subjected to bites of uninfected mosquitoes prior to infectious bites in order to determine whether mosquito bites per se could affect a subsequent P. chabaudi infection. Results: P. chabaudi (ER) infections initiated by mosquito bite were characterized by lower parasitaemia of shorter duration than those observed after direct blood challenge. However, splenomegaly was comparable suggesting that parasitaemia alone does not account for the increase in spleen size. Total numbers of CD4 T cells and those producing IFN-γ, IL-10 and IL-2 were reduced in comparison to direct blood challenge. By contrast, the reduction in IL-4 producing cells was less marked suggesting that there is a proportionally lower Th1-like response in mice infected via infectious mosquitoes. Strikingly, pre-exposure to bites of uninfected mosquitoes reduced the magnitude and duration of the subsequent mosquito-transmitted infection still further, but enhanced the response of CD4 T cells producing IFN-γ and IL-4. Conclusion: The data in this paper suggest that studying early host responses in blood stage malaria infections measured after direct blood challenge of mice may not completely reflect the natural situation, and more detailed investigations of blood-stage immunity after mosquito transmission in experimental models should be considered. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

This paper reviews the pathogenesis of psoriasis, in particular, the immunological cascade in psoriasis. Psoriasis is an immune-mediated skin disease where the T cell plays a pivotal role in the pathogenesis of the disease. The critical steps involved in the pathogenesis include Langerhans cell activation and maturation by antigens in the skin, activation of the T cell by mature Langerhans cells, differentiation and expansion of T cells within the lymph nodes, trafficking of activated T cells from the lymph node to the skin and the subsequent release of cytokines. These cytokines are responsible for epidermal and vascular hyperproliferation and pro-inflammatory effects. Each of these steps provides an opportunity for biological agents designed to block the psoriatic immunological cascade. This paper reviews the immunopathogenesis of psoriasis. Biologic agents in psoriasis, to be published separately, reviews the new biologic therapies that aim to selectively block the immunological steps implicated in the pathogenesis of psoriasis outlined in this paper. [ABSTRACT FROM AUTHOR]

This section presents abstracts of oncology-related topics including the kinetics of tumor growth, the effectiveness of bevacizumab in reducing the growth rate of renal carcinoma and the role of beta-catenin in regulating acute adult T cell leukemia/lymphoma.

The article presents abstracts of research papers related to head and neck surgery, which were presented at the seventy-fifth annual meeting of the German Society for Oto-Rhino-Laryngology. The meeting was held from May 19, 2004 to May 23, 2004 in Bad Reichenhall, Germany. One of the research papers was related to tumor-reactive memory T cells in head and neck cancer patients. Optimization of cancer vaccine trials for the treatment of head and neck cancer depends mainly on tumor-reactive T lymphocytes.

A list of articles related to immunology research are presented. They include "Dose dependent modulation of CD8 and functional avidity as a result of peptide encounter," "Expression of 5-lipoxygenase (5-LOX) in T lymphocytes," and "Salmonella-induced SipB-independent cell death requires TLR4 signalling via the adapter proteins Tram and Trif."

The direct protein-protein interaction between the phosphatase calcineurin and transcription factor NFAT plays important roles in a number of crucial mammalian cell signaling and regulatory events, such as activation of T cells and developmental genetic programs. In this paper, we report on the identification of small organic molecules for the targeted disruption of the NFAT-calcineurin interaction in vitro. In the preceding paper (2l), we devise a theoretical and procedural framework for high-throughput fluorescence polarization screens to aid in this effort. The results presented here ground on this work and illustrate the stringency and successful general applicability of our approach. The identified compounds provide valuable molecular tools for probing calcineurin signaling and for the NFAT-specific inhibition of calcineurin in cells and organisms. [ABSTRACT FROM AUTHOR]

The article presents a list of articles related to immunology. The articles include "Monocyte-Derived Dendritic Cells From Horses Differ From DC of Humans and Mice," by Susanne Mauel, Falko Steinbach and Hanns Ludwig, "Extended Sequence Preferences for Oligodeoxyribonucleotide Activity," by Peter Lenert, Adam Goeken and Robert Ashman, "On the Logic of Positive Selection," by Melvin Cohn, "CTLA-4 Interacts With Stat5 and Inhibits Stat5-Mediated Transcription," by M. Srahna, L. Van Grunsven, J. Remacle and Peter Vandenberghe, and "Peritoneal Macrophages Supress T Cell Activation by Amino Acid Catabolism," by R. Matlack, K. Yeh, L. Rosini, D. Gonzalez, J. Taylor, D. Silberman, A. Pennello and James Riggs.

This paper describes a bi-specific antibody, which was called BIS20×3. It retargets CD3ε-positive cells (T-cells) to CD20-positive cells and was obtained by hybrid-hybridoma fusion. BIS20×3 could be isolated readily from quadroma culture supernatant and retained all the signalling characteristics associated with both of its chains. Cross-linking of BIS20×3 on Ramos cells leads to DNA fragmentation percentages similar to those obtained after Rituximab-cross-linking. Cross-linking of BIS20×3 on T-cells using cross-linking F(ab′)2-fragments induced T-cell activation. Indirect cross-linking of T-cell-bound BIS20×3 via Ramos cells hyper-activated the T-cells. Furthermore, it was demonstrated that BIS20×3 effectively re-targets T-cells to B-cells, leading to high B-cell cytotoxicity. The results presented in this paper show that BIS20×3 is fully functional in retargeting T-cells to B-cells and suggest that B-cell lymphomas may represent ideal targets for T-cell retargeting bi-specific antibodies, because the retargeted T-cell is maximally stimulated in the presence of B-cells. Additionally, since B-cells may up-regulate CD95/Fas expression upon binding of CD20-directed antibodies, B-cells will become even more sensitive for T-cell mediated killing via CD95L/FasL, and therefore supports the intention to use T-cell retargeting bi-specific antibodies recognizing CD20 on B-cell malignancies as a treatment modality for these diseases. [ABSTRACT FROM AUTHOR]

Reveals topics in the forthcoming issues of the journal "Immunology". Impact of cyclic adenylic acid on T cell response; Architecture of secondary lymphoid tissue in sheep; Calcium influx shutdown during neutrophil apoptosis.

A recent paper by Shi et al. defines the role of regulatory T cells (Tregs) in white matter recovery after ischemic stroke. This study elucidates the mechanisms by which Tregs direct microglia to alter their phenotype to support oligodendrogenesis, thereby improving white matter integrity and functional recovery after stroke in mice. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

One of the most used biospecimens in immunology are peripheral blood mononuclear cells (PBMC). PBMC are particularly useful when evaluating immunity through responses of circulating B- and T-cells, during an infection, or after a vaccination. While several reviews and research papers have been published aiming to point out critical steps when sampling, isolating, and cryopreserving human PBMC -or even analyzing any parameter before sampling that could impair the immune assays' outcomes-, there are almost no publications in swine research dealing with these topics. As it has been demonstrated, several factors, such as stress, circadian rhythmicity, or the anticoagulant used have serious negative impact, not only on the separation performance of PBMC, but also on the ulterior immune assays. The present review aims to discuss studies carried out in humans that could shed some light for swine research. When possible, publications in pigs are also discussed. The main goal of the review is to encourage swine researchers to standardize protocols to obtain, manage and preserve porcine PBMC, as well as to minimize, or at least to consider, the bias that some parameters might induce in their studies before, during and after isolating PBMC. [ABSTRACT FROM AUTHOR]

Many researchers are trying to create a low power, high stability, and high-speed static random access memory (SRAM) cell. This paper introduces an SRAM cell consisting of 12 transistors (12 T) developed by carbon nanotube field-effect transistor (CNTFET) to support such an endeavor and be a milestone in creating a better SRAM cell. The proposed 12 T CNTFET SRAM cell is a modified Schmitt-trigger (ST)-based SRAM cell design. The ST-based SRAM cell feedback-cutting and single-ended read decupled techniques are introduced to improve the SRAM cell's static noise margin (SNM) and access time. The presence of stacked N-CNTFETs reduces the proposed cell's power consumption. In addition to conventional 6 T [9] and 8 T [10] SRAM cells, it has been compared with some of the existing SRAM cells such as 12 T SRAM [11] , 12 T SRAM [12] , 12 T SRAM [13] and 12 T SRAM [14] , for calculating the relative performance of the proposed 12 T CNTFET SRAM cell design in terms of fundamental design metrics. The simulation results at 0.9 V show that compared to the afromentioned bit cells, the proposed design accomplishes low power consumption while writing, reading, and holding modes of operation. It has a high SNM during all the operations. The proposed cell has the least read access time. The power, SNM, and access time performance of the bit cells are evaluated for the variation of CNTFET parameters and reported in this article. The proposed cell is also implemented using MOSFET, and the performance of MOSFET and CNTFET is compared. The simulation is done with the HSPICE simulation tool using the Stanford University 32 nm CNTFET model. [ABSTRACT FROM AUTHOR]

Cluster of differentiation 38 (CD38) is a multifunctional extracellular enzyme on the cell surface with NADase and cyclase activities. CD38 is not only expressed in human immune cells, such as lymphocytes and plasma cells, but also is abnormally expressed in a variety of tumor cells, which is closely related to the occurrence and development of tumors. T cells are one of the important immune cells in the body. As NAD consuming enzymes, CD38, ART2, SIRT1 and PARP1 are closely related to the number and function of T cells. CD38 may also influence the activity of ART2, SIRT1 and PARP1 through the CD38-NAD+ axis to indirectly affect the number and function of T cells. Thus, CD38-NAD+ axis has a profound effect on T cell activity. In this paper, we reviewed the role and mechanism of CD38+ CD4+ T cells / CD38+ CD8+ T cells in cellular immunity and the effects of the CD38-NAD+ axis on T cell activity. We also summarized the relationship between the CD38 expression level on T cell surface and disease prediction and prognosis, the effects of anti-CD38 monoclonal antibodies on T cell activity and function, and the role of anti-CD38 chimeric antigen receptor (CAR) T cell therapy in tumor immunity. This will provide an important theoretical basis for a comprehensive understanding of the relationship between CD38 and T cells. [Display omitted] • As a NAD consuming enzyme, CD38 is closely related to the number and function of T cells. • The expression of CD38 in CD4+ T cells and CD8+ T cell affects the function of CD4+T cell. • The expression level of CD38 on T cell surface is associated with disease prediction and prognosis. [ABSTRACT FROM AUTHOR]