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Recent experimental results show that even brief stimulation with antigen can cause antigen-specific CD8 T-cells to undergo sustained proliferation followed by differentiation into memory cells. These results show that the dynamics of these immune responses are not governed by constant monitoring of antigen levels, but rather that following stimulation immune cells commit to a “program”. At present relatively little is known about the program which governs CD8 cell proliferation and differentiation. For example, we do not know whether the program is completely specified by the initial encounter of a T cell with antigen, or whether it subsequently can be modified by the amount of antigen present. Nor do we know whether the entire program for T cell proliferation and differentiation resides within the T cell itself, or whether some component(s) of the program are determined by cells or molecules external to the CD8 cell. In this paper we construct simple mathematical models which incorporate antigen-independent proliferation and differentiation of CD8 cells during acute infections. We use these models to determine what characteristics the program must have in order to be consistent with the existing data on the dynamics of CD8 responses, and in particular to answer the questions posed above. Our results suggest that the program is not completely defined by the initial encounter of T cell with antigen but may be augmented by exposure to antigen in a brief window shortly after infection; furthermore, parts of the program may reside external to the T-cells. Finally we examine some of the consequences of the “program” for pathogen–host coevolution. [Copyright &y& Elsevier]

Antigen recognition by the adaptive cellular immune system is based on a diverse repertoire of antigen receptors. Since this repertoire is formed by genetic recombination, a number of receptors are autoreactive by chance, giving rise to the threat of autoimmune disease. Potentially autoreactive T lymphocytes (T cells) are rendered ineffective by various tolerance mechanisms. One of these mechanisms is negative selection, the deletion from the repertoire of immature autoreactive T cells in the thymus. The present paper shows how to assess the contribution made by negative selection relative to other tolerisation mechanisms by deducing the impact of negative selection on the T cell repertoire from the statistics of autoantigen presentation in the thymus. [ABSTRACT FROM AUTHOR]

T-cell activation and the development of efficient immune responses requires the delivery, by the antigen-presenting cell, of two distinct signals. The first results from the engagement of the TCR:CD3:CD4 complex, and the second from the interaction of CD28 with the B7 family of co-stimulatory molecules. In this context, the physiological significance and the functional consequences of antigen presentation by B7-deficient parenchymal cells, which express MHC class II molecules as a result of inflammation, remains a matter of debate. In this paper we have attempted to critically review the often conflicting reports on the functional effects of antigen presentation by epithelial and endothelial cells to T cells, both in vitro and in vivo. Our own findings are summarised in a model which is consistent with the suggestion of an important role for antigen presentation by parenchymal cells in the induction and the maintenance of peripheral tolerance. [ABSTRACT FROM AUTHOR]

Peripheral lung tissue contains large numbers of T cells, strategically located for immune surveillance at the blood-air interface. Given the intensity of antigenic exposure at this site, it is clear that local T-cell activation events require strict control, in order to maintain tissue homeostasis. How this control is achieved in this unique tissue microenvironment is unknown, and the present study sought to elucidate the process via detailed analysis of the surface phenotypic characteristics of freshly isolated lung T cells. We report below that these cells display typical characteristic of ‘postactivation’, notably elevated basal Ca2+ concentrations, down-modulated T-cell receptors, expression of Ia and ‘late’ activation antigens and concomitant CD4/CD8. However, levels of interleukin-2 receptor and CD2 expression were below those expected of ‘activated’ T-cell populations, and virtually all of the cells were found to be in the G0/G1 phases of the cell cycle. These properties bear a remarkable similarity to those of T cells activated in the presence of endogenous tissue (alveolar) macrophages from the lung (see accompanying paper). We hypothesize that they reflect the in vivo operation of an endogenous macrophage-mediated T-cell anergy-induction process, the function of which is to limit the local clonal expansion of T cells in peripheral lung tissue after in situ activation. [ABSTRACT FROM AUTHOR]

Evidence from in vitro studies indicates that immunoglobulin A (IgA) responses are highly T dependent, yet investigations of the requirement for cognate help For IgA responses in tiro have not previously been undertaken. Experiments reported in this paper employ hapten-carrier immunization of individual Peyer's patches (PP), the site of generation of IgA antibody-containing cells (ACC) responding to lumenal antigenic challenge in the intestine, to determine the requirements for T-cell and B-cell priming under normal physiological conditions in vivo. These experiments demonstrate that both hapten-specific B-cell priming and carrier-specific T-cell priming in PP are required for an IgA-specific anti-hapten ACC response in the intestinal lamina propria to subsequent lumenal challenge with hapten-carrier conjugate. These results confirm that IgA B-cell induction in PP requires cognate T-cell help. An IgA ACC response can also be obtained when hapten and carrier priming occur in different PP, providing functional significance for our previous observations that PP-derived T-helper cells are able to migrate between PP after priming. [ABSTRACT FROM AUTHOR]

As perhaps the staunchest advocates of repertoire purging as the central mechanism of immunological tolerance, we note with satisfaction a spate of recent, elegant papers which suggest an intrathymic clonal abortion model as the explanation for at least some examples of T-cell tolerance. This view agrees with the classical formulation of the Billingham-Brent-Medawar school of tolerance as a specific, central failure of immune responsiveness. Repertoire purging within the B-lymphocyte compartment remains much more controversial. There is no doubt that experimental models exist where the B cell is the reversible target of tolerance induction. The question is, in view of the ease of inducing autoantibody formation both in vivo and in vitro, just how relevant are such clonal anergy mechanisms to authentic self-tolerance? Arguments are presented that there must be two windows of tolerance susceptibility in the ontogeny of the B cell; one while it is maturing in the bone marrow, to prevent autoreactivity of high affinity to important accessible self-antigens; and a second soon after activation of pre-memory cells by exogenous antigen, to prevent fortuitous mutations towards high-affinity anti-self-reactivity establishing a forbidden clone. [ABSTRACT FROM AUTHOR]

There is no doubt that HLA-DR molecules are acting as the products of HLA-linked immune response genes (Ir-genes), because (i) HLA-DR molecules are the restriction elements in the interaction between CD4+ helper T cells and antigen-presenting cells (APC) to respond to many antigens such as streptococcal cell wall antigen (SCW) (Nishimura & Sasazuki, 1983; Sone et al., 1985; Hizayama et al., 1986), schistosomal antigen (Sj) (Hirayama et al., 1987), Mycobacterium leprae antigen (ML) (Kikuchi et al., 1986) and so on; and (ii) anti-HLA-DR monoclonal antibodies completely abolish the immune response to those antigens (Nishimura & Sasazuki, 1983; Sone et al., 1985). However, genetic analysis of the immune response to those antigens in families or populations revealed that responsiveness is recessive and non-responsiveness to those antigens is a dominant genetic trait that is tightly linked to HLA (Sasazuki et al., 1980a, 1983; Watanabe et al., 1988). This is completely opposite to the situation under the Ir-gene control where responsiveness is dominant and non-responsiveness is recessive. In this paper, we report evidence of how we came across the concept of HLA-linked immune suppression genes (Is-genes) besides Ir-genes, and show evidence for the epistatic interaction between HLA-DR and DQ to determine the immune response to several antigens in humans. [ABSTRACT FROM AUTHOR]

A panel of monoclonal antibodies (mAb) was developed by the fusion of Sp2/0 myeloma cells and spleen cells from mice immunized with peripheral blood mononuclear cells (PMNC) or T cells from NIH swine leucocyte antigen (SLA) inbred miniature swine. Twenty stable hybridoma clones were isolated that secreted mAb that reacted with swine PMNC, as determined by an enzyme-linked immunosorbent assay (ELISA). The binding profile to swine PMNC and the ability to fix complement of these mAb were investigated by flow cytometric analyses. The molecular weights of the antigens recognized by six of the mAb were determined by immunoprecipitation of 125I-surface-labelled PMNC, followed by SDS-PAGE under reducing conditions. The most interesting mAb, 7-34-1 (IgG2a), precipitated a putative MUC class I molecule composed of a 50,000 MW heavy chain and a 12,000 MW light chain (β2m). This is the third SLA class I-reactive monoclonal antibody to be described for swine. Properties of the mAb described in this paper, mAb 7-34-1, are different from the two other SLA class I-specific mAb that have been described elsewhere in the literature (mAb 74-11-10 and mAb FF85). M onoclonal antibody 7-34-1 recognized class I antigens of SLA haplotypes a, c and din an equivalent manner. This mAb should be especially useful as a general anti- SLA class I reagent for experiments on NIH miniature swine. [ABSTRACT FROM AUTHOR]

In different murine systems, delayed-type hypersensitivity (DTH) swelling responses at 24–48 hr after antigen challenge were preceeded by an early 2-hr swelling response. The 24-hr DTH response is thought to depend on this early (DTH-initiating) hypersensitivity response. In this paper we show that in the syngeneic DBA/2-SL2 routine turnout system only an early 2-hr swelling response can be evoked. This early hypersensitivity response was tumour specific and serotonin dependent. The early hypersensitivity response in contact hypersensitivity has been ascribed to antigen-specific T-cell factors. To test whether similar T-cell factors were involved in the early hypersensitivity response in this syngencic turnout system, we have transferred lymph node, spleen lymphocytes and scram from immunized mice into naive recipients. The serum was fractionated in two fractions, a 50,000–80,000 MW fraction, and a 120,000–190,000 MW fraction. In recipients of lymphocytes, total serum and the 50,000–80,000 MW fraction of the serum, an early hypersensitivity response can be evoked. So, these data suggest the involvement of specific T-cell factors in the development of an early hypersensitivity response against syngeneic tumour cells. Despite the development of an early (DTH initiating) hypersensitivity swelling response these immunized animals cannot develop a classical 24-hr swelling response. This absence of the 24-hr response in the presence of the 2-hr response is discussed in relation to the frequently observed immune suppression in tumour-bearing mice. [ABSTRACT FROM AUTHOR]

The results presented in this paper demonstrate that a mouse IgM monoclonal antibody (T-80) recognizes an antigen on cells of the T-lymphocyte lineage of sheep. However, this antibody does not identify all T cells, as 10-20% of thymocytes and some peripheral-blood T cells are negative. T-80- thymocytes reside in the medulla. The majority of cortical thymocytes are T-80+ and classified as dull cells on the basis of antigen density per cell as measured by flow microfluorometry. In contrast, T-80+ cells in the periphery can be categorized into two populations, i.e., dull cells and bright cells. Suggestive evidence was obtained that bright T-80+ cells are fast recirculating T cells, whereas dull ceils are sessile or less easily mobilizable T cells in the periphery. In foetal environment, over 90% of thymocytes and approximately 5% of spleen cells are T-80+ at 54 days of gestation (gestation period = 150 days), which may indicate that T-cell emigration from the thymus commences well before mid-gestation in sheep. [ABSTRACT FROM AUTHOR]

One of the T suppressor circuits induced by picrylsulphonic acid includes the T suppressor cell (Ts-eff) which acts at the efferent stage of the contact sensitivity reaction and produces antigen-specific T suppressor factor (TsF). This factor does not act directly but arms a T acceptor cell (Tacc). This Tacc liberates a non-specific inhibitor when it is armed with TsF and then exposed to picrylated cells sharing the I-J genotype of the source of the TsF. This paper investigates the role of I-J region gene products in this T suppressor circuit. Two approaches were used. Syngeneic CBA (H-2k) lymphocytes were separated into I-J+ and I-J- cells by treatment with anti-I-Jk serum followed by panning on anti-immunoglobulin plates. The cells were then picrylated and used as a source of antigen. Alternatively, B10.A congeneic mice syngeneic (SR) or allogeneic (3R) with CBA at the I-J locus were picrylated and used similarly. The main findings were as follows. (i) The intravenous injection of picrylated I-J+ spleen cells but not a similar number of I-J- cells induced Ts-eff which blocked the transfer of contact sensitivity. Picrylated unseparated cells syngeneic, but not allogeneic, at the I-J locus were also effective. (ii) It is known that the lymphocytes of mice injected with picrylsulphonic acid and then re-exposed to antigen by painting with picryl chloride liberate TsF in vitro. The re-exposure to antigen can be replaced by the intravenous injection of picrylated I-J+ cells or by cells syngeneic at the I-J locus the day before harvesting the spleen cells. (iii) The release of non-specific inhibitor by Tacc armed with TsF requires exposure to picrylated I-J+ cells or cells syngeneic at the I-J locus. The requirement for antigen on a cell bearing syngeneic I-J suggests that antigen together with I-J is an activation signal in this T-cell circuit. The simplest explanation is that the receptor of the pristine Ts and of the mature Ts-eff is similar to T suppressor factor. [ABSTRACT FROM AUTHOR]

This paper investigates desensitization in vitro, e.g. the inhibition of the transfer of contact sensitivity to picryl chloride by incubation of the passive transfer population with picrylated spleen cells. It asks whether desensitization is based on the same T-suppressor circuit which is responsible for the inhibition of passive transfer by antigen-specific T-suppressor factor (TsF). In this circuit, the T-suppressor cell which acts at the efferent stage (Ts-eff) makes TsF. This TsF depresses contact sensitivity indirectly by arming a T-acceptor cell (Tacc). The armed Tacc, when exposed to antigen (picrylated spleen cells), liberates a non-specific inhibitor which blocks the transfer of contact sensitivity. The three elements of this T-suppressor circuit occur in nylon wool-purified T cells prepared from the lymph nodes and spleens of mice four days after immunization with picryl chloride. This population transfers contact sensitivity and can be desensitized in vitro. It contains Ts-eff which can be isolated by panning (adherence) on picrylated albumin and detected by their ability to inhibit passive transfer. The 24 hr supernatant of cultures of these cells contains TsF. Finally the population contains Tacc which appear in the spleen 2 days after immunization and virtually disappear by 10 days. Further experiments demonstrated that the Ts-eff and the Tacc were not merely present but actually required for desensitization in vitro. Immune cells depleted of both Ts-eff (by panning on picrylated albumin) and Tacc (by arming with anti-oxazolone TsF and panning on oxazolonated albumin) cannot be desensitized. To restore desensitization both Ts-eff and Tacc must be added back. The Ts-eff were characterized as cyclophosphamide resistant, adult thymectomy sensitive cells (Cyr, ATx5), which adhered to antigen and were produced only by specific immunization. The Tacc were characterized as CF5, ATx5 cells which adhered to antigen only after arming with antigen-specific T-suppressor factor and were produced after immunization with an unrelated contact sensitizer, 'oxazolone'. It was concluded that desensitization in vitro was due to the interaction of two distinct T cells: the T-suppressor cell which acts at the efferent stage of the contact sensitivity reaction and the T-acceptor cell which becomes armed with the specific T-suppressor factor produced by the Ts-eff. [ABSTRACT FROM AUTHOR]

In this paper we describe the first in vitro response to the liver alloantigen F. The anti-F response serves as a valuable model for autoimmune phenomena since priming appropriate strains of mice (responders) with allogeneic but not syngeneic type F leads to autoantibody production. The in vitro system is based on the proliferation of T cells, from mice primed in vivo with F, when coincubated with splenic adherent cells (SAC) prepulsed with F in vivo. The system displays two important correlates of the in vivo antibody response to F:1.T cells from mice primed with syngeneic F do not proliferate when incubated with SAC prepulsed with syngeneic F and 2. Mice that do not make antibody responses to allo F in vivo (DBA/2) do not show in vitro proliferative responses. These findings indicate that the proliferative assay is a good in vitro model for the F response. [ABSTRACT FROM AUTHOR]

The binding of EPF to lymphocytes stimulates the release of soluble mediators, active in T cell dependent reactions, namely the rosette inhibition test and the adoptive transfer of contact sensitivity. On the basis of their ability to inhibit the delayed type hypersensitivity reaction in this latter assay, they have been classified as suppressor factors. This paper describes the identification of two EPF-induced suppressor factors. Unlike EPF which is neither species-restricted nor strain-restricted, these factors are genetically restricted in their action in the rosette inhibition test EPF-S1 (estimated Mr 14,000) is restricted to the I region of the mouse MHC, while EPF-S2 (estimated Mr 55,000) is restricted to a locus (or loci) outside the MHC. Like other antigen non-specific factors, release of these suppressor factors can be stimulated also by Con A. [ABSTRACT FROM AUTHOR]

Freshly isolated B cells from chronic lymphocytic leukaemia patients (B-CLL) have been previously shown to induce a strong proliferative response and high levels of NK-like activity in lymphocytes from healthy donors. The present paper deals with the origin, mitotic state, target spectrum and cell surface phenotype of the NK-like effectors generated after stimulation with B-CLL. Experiments using large granular lymphocytes (LGL) and T cells as responders demonstrated that most of the precursors of the newly generated NK-like effectors express the CD3 antigen. The induction of NK-like activity paralleled cell activation, as judged by blast transformation, thymidine uptake and appearance of cell surface activation markers. The newly generated NK-like effectors displayed a T cell phenotype and a broader target repertoire than native NK cells. [ABSTRACT FROM AUTHOR]

The antigen-induced DNA synthesis in vitro in lymphocytes from patients with acute Plasmodium falciparum malaria was investigated. The patients and healthy controls from Sweden or Colombia were the same as those studied in the accompanying paper (Troye-Blomberg el al., 1983). The malarial antigens used were sonicated membrane preparations or purified and concentrated supernatants from in vitro cultures of P. facliparum, similar preparations derived from normal human erythrocytes served as control antigen. In the patients' lymphocytes P. falciparum antigens induced a weak or moderate but significant stimulation of DNA synthesis, peaking after 3-4 days of incubation. This early response was specific for P. faleiparum since it was not obtained with lymphocytes from healthy donors nor with those from patients with acute P. vivax or P. ovale malaria. No antigen-induced response was seen in about half of the P.falciparum patients. However in a few negative eases, available for consecutive testing, positive reactions were seen with lymphocytes taken 2 weeks after infection when the blood of these patients was free of parasites. The early response induced in patients' lymphocytes to the P. falciparum antigens was not obtained with RBC antigen, however, these preparations frequently induced a response rising to significant levels later during incubation (day 5-6)- Similar delayed responses were obtained when either- patients' or control donors' lymphocytes were exposed to the P. falciparum antigens. This indicates that both the RBC and the parasite preparations contained mitogenic substances affecting human lymphocytes in general and easily obscuring the P, falciparum specific responses seen only in the patients. This latter response was relatively low and short lived, suggesting that it reflected a secondary in vitro stimulation of in vivo primed lymphocytes and that it was regulated by suppressor mechanisms. [ABSTRACT FROM AUTHOR]

T follicular helper (Tfh) cells help B cells to generate affinity-matured antibodies. Three papers in this issue of Immunity () provide information about the reciprocal relationship between B cells and Tfh cells. [ABSTRACT FROM AUTHOR]

The entry of exogenous antigen into the MHC class I-restricted crosspresentation pathway can contribute to CD8+ T cell tolerance and immunity, in particular to peripheral self-antigens or selected viruses and bacteria showing restricted tissue tropism. Dendritic cells are the key crosspresenting cells and, as such, they are thought to carry specialized machinery dedicated to this purpose. Two recent papers describe intracellular components tailored to the dendritic cell crosspresentation pathway. [Copyright &y& Elsevier]

Photochemical internalization (PCI) is a further development of photodynamic therapy (PDT). In this report, we describe PCI as a potential tool for cellular internalization of chemotherapeutic agents or antigens and systematically review the ongoing research. Eighteen published papers described the pre-clinical and clinical developments of PCI-mediated delivery of chemotherapeutic agents or antigens. The studies were screened against pre-defined eligibility criteria. Pre-clinical studies suggest that PCI can be effectively used to deliver chemotherapeutic agents to the cytosol of tumor cells and, thereby, improve treatment efficacy. One Phase-I clinical trial has been conducted, and it demonstrated that PCI-mediated bleomycin treatment was safe and identified tolerable doses of the photosensitizer disulfonated tetraphenyl chlorin (TPCS2a). Likewise, PCI was pre-clinically shown to mediate major histocompatibility complex (MHC) class I antigen presentation and generation of tumor-specific cytotoxic CD8+ T-lymphocytes (CTL) and cancer remission. A first clinical Phase I trial with the photosensitizer TPCS2a combined with human papilloma virus antigen (HPV) was recently completed and results are expected in 2020. Hence, photosensitizers and light can be used to mediate cytosolic delivery of endocytosed chemotherapeutics or antigens. While the therapeutic potential in cancer has been clearly demonstrated pre-clinically, further clinical trials are needed to reveal the true translational potential of PCI in humans. [ABSTRACT FROM AUTHOR]

The intracellular peptide pump TAP feeds antigenic peptides for loading onto HLA class I molecules, and its down-modulation is a frequent immune evasion mechanism in human cancers. Two recent papers describe which 'hidden' antigens we might exploit to target these escaped cancer variants by CD8 T cells. These unTAPped peptides are now ready for clinical testing. [ABSTRACT FROM AUTHOR]

Langerhans cells (LCs) represent a unique DC subset populating the outermost body surface, i.e., the epidermis. Although CDla and langerin (CD207) are used as specific markers to distinguish LCs from other DC subsets, their immunological functions have remained mostly unknown. A new paper (see the related article beginning on page 701) demonstrates that LCs utilize these markers to induce cellular immune responses to Mycobacterium leprae: CDla mediates the presentation of nonpeptide antigens to T cells, while langerin facilitates uptake of microbial fragments and perhaps their delivery to a specialized subcellular compartment. [ABSTRACT FROM AUTHOR]

Previous work has established that whereas X/X mice carrying the sex-reversing chromosomal fragment Sxr are positive for the male-specific transplantation antigen, H-Y, X/X mice carrying the variant Sxr', although they too develop as phenotypic males, are H-Y negative. In this paper we show that X/XSxr' male mice do not express any male-specific antigen that can induce skin-graft rejection. [ABSTRACT FROM AUTHOR]

Epidermal Langerhans cells are dendritic bone marrow-derived cells which synthesize and express Ia antigens. During the past decade, in vitro studies have demonstrated that they play a critical role in the induction of many types of T-cell responses. Specifically, Langerhans cells are effective antigen-presenting cells in allogeneic and antigen specific proliferative and cytotoxic T-cell responses. This paper reviews these functions and suggests areas of future investigations into the mechanisms involved in T-cell activation by Langerhans cells. [ABSTRACT FROM AUTHOR]

The article discusses two research papers concerned with how subsets of T cells that mediate acute and long-term protection to infection are derived from a single precursor. Effector cells are short-lived and numerous T cells that can deploy a variety of cytokine and cell contact-dependent cytotoxic mechanisms to control acute infection. Memory T cells effectively respond to reinfection by the same pathogen. These are both subsets of CD8+ cells. One paper shows that the T cell receptor, which is a heterodimeric protein that serves as the antigen-specific sensor for T cells, helps to generate the signals that allow a primed T cell to differentiate into a memory cell.

High titer of anti-β2-glycoprotein I antibodies (anti-β2GPI Ab) plays a pathogenic role in antiphospholipid syndrome (APS). Numerous studies have focused on the pathological mechanism in APS; however, little attention is paid to the immune mechanism of production of anti-β2GPI antibodies in APS. Our previous study demonstrated that Toll-like receptor 4 (TLR4) plays a vital role in the maturation of bone marrow-derived dendritic cells (BMDCs) from the mice immunized with human β2-glycoprotein I (β2GPI). TLR4 is required for the activation of B cells and the production of autoantibody in mice treated with β2GPI. However, TLR4 provides a third signal for B cell activation and then promotes B cells better receiving signals from both B cell antigen receptor (BCR) and CD40, thus promoting B cell activation, surface molecules expression, anti-β2GPI Ab production, and cytokines secretion and making B cell functioning like an antigen presenting cell (APC). At the same time, TLR4 also promotes B cells producing antibodies by upregulating the expression of B-cell activating factor (BAFF). In this paper, we aim to review the functions of TLR4 in B cell immune response and antibody production in autoimmune disease APS and try to find a new way for the prevention and treatment of APS. [ABSTRACT FROM AUTHOR]

Human genetic and environmental factors underlie susceptibility to the T cell-mediated autoimmune disease, multiple sclerosis (MS). How the environment influences the pathogenesis of MS has been difficult to parse. A recent paper in Cell shows that environmental antigens that activate myelin-specific T cells can be identified with unprecedented accuracy. [Copyright &y& Elsevier]

Background. CD8+ T cells have putative roles in the regulation of adaptive immune responses during infection. The purpose of this paper is to compare the status of CD8+ T cells in Multiple Sclerosis (MS) and Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). Methods. This preliminary investigation comprised 23 CFS/ME patients, 11 untreated MS patients, and 30 nonfatigued controls. Whole blood samples were collected from participants, stained with monoclonal antibodies, and analysed on the flow cytometer. Using the following CD markers, CD27 and CD45RA (CD45 exon isoform 4), CD8+ T cells were divided into naïve, central memory (CM), effector memory CD45RA- (EM), and effector memory CD45RA+ (EMRA) cells. Results. Surface expressions of BTLA, CD127, and CD49/CD29 were increased on subsets of CD8+ T cells from MS patients. In the CFS/ME patients CD127 was significantly decreased on all subsets of CD8+ T cells in comparison to the nonfatigued controls. PSGL-1 was significantly reduced in the CFS/ME patients in comparison to the nonfatigued controls. Conclusions. The results suggest significant deficits in the expression of receptors and adhesion molecules on subsets of CD8+ T cells in both MS and CFS/ME patients. These deficits reported may contribute to the pathogenesis of these diseases. However, larger sample size is warranted to confirm and support these encouraging preliminary findings. [ABSTRACT FROM AUTHOR]

The article offers information from the original research papers on T cells and helper cell metamorphosis, "T follicular helper cells differentiate from Th2 cells in response to helminth antigens," by A.G. Zaretsky et al. and "IL-4ߝproducing CD4+ T cells in reactive lymph nodes during helminth infection are T follicular helper cells," by I.L. King and M. Mohrs that appeared in the April 20, 2009 issue of the "Journal of Experimental Medicine."

The article presents abstracts of research papers about myelin genes and autoimmunity. They include "A role for myelin and nonmyelin autoantibodies in the pathogenesis of demyelinating disease," "Autoimmune T cell response to myelin antigens: building better animal models for MS," "Tolerance induction of MBP-specific T cells," and "Golli protein negatively regulates store-depletion-induced calcium influx in T cells."

The article presents abstracts of research papers on relapse in multiple sclerosis and its relation to the peripheral and central immune system. They include "Interaction between systemic inflammation and brain inflammation in chronic neurodegeneration," "Molecular mechanisms of T cell migration across the blood-brain barrier," "Antigen presentation during autoimmune CNS inflammation: killers, victims and the snitch who plays them both!," and "Glial cells as inducers of immune cell entry and activation in the brain."

The article lists several research papers selected by the editors of the journal which includes topics related to immunogenicity of differentiated cells derived from pluripotent cells, generation of rejuvenated antigen-specific T cells and regeneration of human tumor antigen-specific T cells.

The article presents research highlights from the field of T cell memory based on the original research paper "Professional memory CD4+ T lymphocytes preferentially reside and rest in the bone marrow," by K. Tokoyoda et al. that was published in the May 7, 2009 issue of "Immunity." Subjects discussed include antigen-specific memory T cells in mice, immune responses, and the role of interleukin-7 (IL-7) in expressing stromal cells.

Based on the functions and some relevant theories of the biological immune system, an artificial immune system is established to solve the practical problems for computing systems. At present, the artificial immune system includes two major categories: the mechanism of non-self recognition and immune network, the most important of which is negative selection algorithm. The negative selection algorithm is proposed to simulate the formation and running mechanism of T cells for the immune system in 1994. In this algorithm, one of the key steps is the detector generation. Unfortunately, the current detector generating algorithms have detector generation inefficiencies, holes area, and redundant detector problems to some degree. In this paper, from the perspective of one dimension, a novel detector generating algorithm that is based on interval partition is proposed. At the beginning of this algorithm, we make the maximal interval be the initial detector; second, this detector should experience the training of self-tolerance. According to the matching rule, we let this detector match the given collection of selves; then we remove the points from the interval detector which matches the selves. At the same time, we divide the interval into two parts at this point and have the candidate detectors optimized by the corresponding interval collations and amalgamations. That is to say, the initial detector interval is divided recursively according to the spatial locations of selves. At last, we can get a set of excellent mature detectors, which can be used to protect the system security. To illustrate the advantage of this algorithm, we have given an example. From this example, we can declare that the algorithm improves the current detector generations and matching rules greatly. It also helps to remove the holes area and redundant detectors. Therefore, both the detector generation efficiency and the detecting efficiency are well improved. By the theoretical analysis and comparison, the system can detect a large number of non-self antigens only using a small quantity of detectors. Obviously, the algorithm achieves the high non-self identification system. [ABSTRACT FROM AUTHOR]