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Lymph nodes are traditionally regarded as having three compartments, the cortex, paracortex and medulla. B and T cells home to separate areas within these compartments, interact with antigen presenting cells, and undergo clonal expansion. This paper provides structural and functional details about how the lymph node brings lymphocytes and antigen presenting cells together. The concept of the lymphoid lobule as the basic functional and anatomic unit of the lymph node is developed and utilized to provide a framework for understanding lymph node pathobiology. Understanding the histomorphologic features of the lymphoid lobule and the role of the reticular meshwork scaffolding of the lymph node and how these related to the cortex, paracortex and medulla provides a unique approach to understanding lymph node structure and function. [ABSTRACT FROM AUTHOR]

In 1955, he defended his PhD on hormones and infection and started working at the Institut Pasteur (Paris) in the laboratory of Therapeutic Chemistry under André Lamensans. Graph Louis Selim Chedid was born in Cairo (Egypt) in June 1922 and died in Paris in March 2021 at the age of 98. 10 Leclerc C, Bahr GM, Chedid L. Marked enhancement of macrophage activation induced by synthetic muramyl dipeptide (MDP) conjugate using monoclonal anti-MDP antibodies. [Extracted from the article]

Objectives: Allergen immunotherapy is the only cure for immunoglobulin E mediated type I respiratory allergies. Subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are the most common treatments. In this article, we reviewed new routes of allergen immunotherapy. Methods: Data on alternative routes to allow intralymphatic immunotherapy (ILIT), epicutaneous immunotherapy (EPIT), local nasal immunotherapy (LNIT), oral immunotherapy (OIT), and oral mucosal immunotherapy (OMIT) were gathered from the literature and were discussed. Results: ILIT features direct injection of allergens into lymph nodes. ILIT may be clinically effective after only a few injections and induces allergen-specific immunoglobulin G, similarly to SCIT. A limitation of ILIT is that intralymphatic injections are required. EPIT features allergen administration by using patches mounted on the skin. EPIT seeks to target epidermal antigen-presenting Langerhans cells rather than mast cells or the vasculature; this should reduce both local and systemic adverse effects. LNIT involves the spraying of allergen extracts into the nasal cavity. Natural or chemically modified allergens (the latter, termed allergoids, lack immunoglobulin E reactivity) are prepared in a soluble form. OIT involves the regular administration of small amounts of a food allergen by mouth and commences with low oral doses, which are then increased as tolerance develops. OMIT seeks to deliver allergenic proteins to an expanded population of Langerhans cells in the mucosa of the oral cavity. Conclusions: ILIT, EPIT, LNIT, OIT, and OMIT are new routes for allergen immunotherapy. They are safe and effective. [ABSTRACT FROM AUTHOR]

In humans and mouse models, Foxp3+ regulatory T cells are known to control all aspects of immune responses. However, only limited information exists on these cells’ role in diseases of other animals. In this review, we cover the most important features and different types of regulatory T cells, which include those that are thymus-derived and peripherally induced, the mechanisms by which they control immune responses by targeting effector T cells and antigen-presenting cells, and most important, their role in animal health and diseases including cancer, infections, and other conditions such as hypersensitivities and autoimmunity. Although the literature regarding regulatory T cells in domestic animal species is still limited, multiple articles have recently emerged and are discussed. Moreover, we also discuss the evidence suggesting that regulatory T cells might limit the magnitude of effector responses, which can have either a positive or negative result, depending on the context of animal and human disease. In addition, the issue of plasticity is discussed because plasticity in regulatory T cells can result in the loss of their protective function in some microenvironments during disease. Lastly, the manipulation of regulatory T cells is discussed in assessing the possibility of their use as a treatment in the future. [ABSTRACT FROM AUTHOR]

Background: Mitoxantrone has been approved for patients with worsening relapsing--remitting (RR) or secondary progressive multiple sclerosis (SPMS), but its long-term use is limited by its cardiotoxicity. Pixantrone (PIX) is an analog of mitoxantrone. Objectives: The aim of this open-label, multicenter, noncomparative Phase I/II trial was to explore the immunosuppressive effect of PIX, its impact on clinical disease activity and cerebral gadoliniumenhanced (Gd+) lesions, and its safety. Methods: Eighteen patients with active RRMS and SPMS (≥ 1 cerebral Gd+ lesion) despite approved immunomodulatory therapy received four intravenous PIX injections every 21 days. A neurological examination, hematology, lymphocyte subsets, and biochemistry were performed at Day 1, Weeks 3, 6 and 9, and Months 3, 6, 9 and 12. Echocardiography was performed before each infusion, at Months 3, 6 and 12. Cerebral MRI was performed at baseline, and at Months 6 and 12. Results: CD19+ cells were reduced by 95% at Month 3 and by 47% at Month 12. Gd+ lesions were reduced by 86% at Month 12 (p = 0.01). The annual relapse rate was reduced by 87% (p < 10-4). Two patients experienced a transient reduction in left ventricular fraction. Conclusion: These preliminary data indicate the efficacy of PIX in active RRMS and SPMS. [ABSTRACT FROM AUTHOR]

The article presents a study which investigates the activation of CD4+ T cells, monocytes and dendritic cells (DC) in multiple sclerosis (MS) patients treated with glatiramer acetate (GA). The cross-sectional study used flow cytometry to assess the activation of CD4+ T cells, monocytes and DC of 39 untreated and 29 GA-treated MS patients in relation to disease activity. Results showed that prominent changes in circulating antigen-presenting cells and CD4+ T cells in MS patients treated with GA.

The article offers information on a research that analyzes the effect of 7T magnetic resonance imaging technique in the diagnosis of multiple sclerosis (MS). It is mentioned that five patients with MS were serially scanned for around 2.5 years at 7T using high resolution gradient-echo sequence. It was observed that ring phase lesions remained unchanged over 2.5 years which contrasts the notion that acute activated iron-rich macrophages reside in such lesions.

Persistent infections with human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) are a major cause of morbidity and mortality worldwide. As sentinels of our immune system, dendritic cells (DCs) play a central role in initiating and regulating a potent antiviral immune response. Recent advances in our understanding of the role of DCs during HIV-1 and HCV infection have provided crucial insights into the mechanisms employed by these viruses to impair DC functions in order to evade an effective immune response against them. Modulation of the immunological synapse between DC and T-cell, as well as dysregulation of the crosstalk between DCs and natural killer (NK) cells, are emerging as two crucial mechanisms. This review focuses on understanding the interaction of HIV-1 and HCV with DCs not only to understand the immunopathogenesis of chronic HIV-1 and HCV infection, but also to explore the possibilities of DC-based immunotherapeutic approaches against them. Host genetic makeup is known to play major roles in infection outcome and rate of disease progression, as well as response to anti-viral therapy in both HIV-1 and HCV-infected individuals. Therefore, we highlight the genetic variations that can potentially affect DC functions, especially in the setting of chronic viral infection. Altogether, we address if DCs' potential as critical effectors of antiviral immune response could indeed be utilized to combat chronic infection with HIV-1 and HCV. [ABSTRACT FROM AUTHOR]

To determine the origin of peripheral blood mononulclear cells (PBMC) that activate regulatory T cells in anterior chamber- associated immune deviation (ACAID), fluorescein-labeled PBMC were intravenously injected into mice before the mice received an intracameral injection of antigen. Six-24 hr after intracameral injection, fluorescein-labeled PBMC increased in the iris. Twenty- four-48 hr labeled cells decreased in the iris and increased in the thymus and spleen. The entry of the labeled PBMC into the anterior chamber and subsequent production of PBMC that transfer ACAID required the expression of CCR2 by the PBMC and the production of the chemokine CCL2 by the recipient of the PBMC. The results suggest that the intracameral injection of antigen induces i) the infiltration of F4/80+ PBMC into the AC, ii) where these PBMC are converted to a regulatory phenotype, and iii) recirculate to activate T cells that suppress cell-mediated immunity. [ABSTRACT FROM AUTHOR]

Different immunological alterations may condition systemic lupus erythematosus (SLE) activity. However, it is not known whether alterations in the phenotype of circulating antigen-presenting cells (APCs) and in the response to CpG oligodeoxynucleotides (ODN-CpG) correlate with disease activity. APC expression of HLA-DR, costimulatory molecules, and TLR9 expression was determined in patients with SLE, other autoimmune diseases, and healthy controls.Monocyte and B cell response to synthetic ODN-CpG sequences was also evaluated. Monocytes from patients with moderate SLE activity had higher expression of CD40 and CD86. Decreased numbers of CD19+ CD80+ and BDCA-3+CD40+ cells were found in patients with severe SLE activity. In patients with moderate SLE activity, non-adherent and enriched B cell response to ODN-CpG was similar to healthy controls. Adherent and enriched B cells from patients with severe SLE activity did not increase costimulatory molecule expression or cytokine production after ODN-CpG stimulation. APCs frompatients with SLE, regardless of disease activity, displayed higher percentage of TLR9+ cells, as well as increased expression of TLR9, compared to healthy controls. Results suggest that the B cell response to ODN-CpG correlates with the SLE activity, independently of TLR9 expression, indicating that alterations in B cell response in severe activity SLE may be caused by events down-stream to TLR9. [ABSTRACT FROM AUTHOR]

The composition and location of professional antigen presenting cells (APC) varies in different mucosal surfaces. The cornea, long considered an immune-privileged tissue devoid of APCs, is now known to host a heterogeneous network of bone marrow-derived cells. Here, we utilized transgenic mice that express enhanced green fluorescent protein (EGFP) from the CD11c promoter (pCD11c) in conjunction with immunohistochemical staining to demonstrate an interesting stratification of APCs within non-inflamed murine corneas. pCD11c+ dendritic cells (DCs) reside in the basal epithelium, seemingly embedded in the basement membrane. Most DCs express MHC class II on at least some dendrites, which extend up to 50 μm in length and traverse up 20 μm tangentially towards the apical surface of the epithelium. The DC density diminishes from peripheral to central cornea. Beneath the DCs and adjacent to the stromal side of the basement membrane reside pCD11c-CD11b+ putative macrophages that express low levels of MHC class II. Finally, MHC class II-pCD11c-CD11b+ cells form a network throughout the remainder of the stroma. This highly reproducible stratification of bone marrow-derived cells is suggestive of a progression from an APC function at the exposed corneal surface to an innate immune barrier function deeper in the stroma. [ABSTRACT FROM AUTHOR]

Dendntic cells (DCs) are functionally abnormal in systemic lupus erythematosus (SLE). However, previous studies have involved in-vitro cytokine-induced DCs. In this investigation, directly isolated circulating plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) in SLE were studied. Blood dendritic cell antigen (BDCA)-4 and BDCA-1 magnetic isolation kits were used to isolate blood pDCs and mDCs from 30 SLE patients and 36 controls. Their number and surface markers, and their relationship with lupus disease activity were evaluated. The percentage of pDCs per peripheral blood mononuclear cells was higher in SLE (0.33 ± 0.14) than in controls (0.16 ± 0.09, P <0.01), but that of mDCs was lower in SLE (0.43 ± 0.14) than in controls (0.63 ± 0.32; P < 0.01). In controls, both pDCs and mDCs expressed high levels of MHC-II, however, the expression of CD86, CD83 and CCR7 on pDCs were significantly lower than that on mDCs (all P < 0.05). mDCs from patients with SLE, particularly those with active disease, expressed lower CD83 than controls. In health, circulating mDCs may be more efficient than pDCs in stimulating T cells. In SLE, the increased number of circulating pDCs supports a pathogenic role for these cells, and the decreased mDC number and CD83 expression may explain the susceptibility to infections in these patients. [ABSTRACT FROM AUTHOR]

Genetic determinants taking part in the development of systemic lupus erythematosus (SLE) are complex and not fully characterized. Dysregulated expression of genes involved in the control of apoptosis has been previously suggested. We report here a consanguineous family with SLE manifestations in three siblings associated in one of them with severe lymphoproliferative features. Laboratory studies showed no defect in CD95-mediated cell death. Screening expression of Bcl-2 family genes that regulate mitochondrial apoptosis pathway showed an overexpression of the antiapoptotic Bfl-1 gene. Real time RT-PCR analysis indicated that overexpression of Bfl-1 was restricted to B-cells, with normal expression in T-cells. Those results suggest that overexpression of Bfl-1 could result in impaired B-lymphocyte homeostasis and inappropriate immune response leading to autoimmune manifestations. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can be exacerbated by exposure to ultraviolet radiation (UVR). The number and phenotype of antigen presenting cells in the skin play a role in cutaneous immune response generation. Although antimalarials are widely used in SLE treatment, their mode of action is not completely elucidated. The aim of our study was to determine the effect of chloroquine treatment on HLA-DR+ and CD1a+ cell number in locally irradiated (three minimal erythema doses of UVB) and normal appearing skin in SLE patients and healthy subjects. A significantly higher number of HLA-DR+ and CD1a+ cells were found in both locations in SLE patients compared with controls. Following three months of daily chloroquine treatment (250 mg), the HLA-DR+ and CD1a+ cell counts were significantly reduced in both irradiated and unirradiated sites of SLE patients, although still higher than in controls. Chloroquine treatment reduces the number of antigen presenting cells in the skin of SLE patients, and this effect may explain the antimalarials beneficial immunoregulatory and anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

CD80 and CD86, expressed on the antigen-presenting cells (APCs) provide costimulatory signals for T lymphocytes. Recently, defective expression of CD80 has been reported in systemic lupus erythematosus (SLE) although its mechanism is unclear. Here, expression of the B7 antigens induced by interferon-γ, interleukin-4 or granulocyte-macrophage stimulating-factor (GM-CSF) along the differentiation process of APCs was investigated. In contrast to CD86, expression of CD80 on the CD14[sup +] cells induced by GM-CSF was reduced in SLE. GM-CSF receptor (GMCSFR) was down-regulated by GM-CSF or phorbol 12-myristate 13-acetate in both of the normal controls and SLE patients, while this change was more remarkable in the latter. In the presence of 1-(5-isoquinolinsulfonyl)-2-methylpiperazine, an inhibitor of protein kinase C, the PMA-induced down-regulation of GM-CSFR was reversed in the normal controls but not in SLE. These data suggest that dysregulation of the GM-CSFR might be associated with the defective expression of CD80, leading to dysfunction of the APCs in SLE. [ABSTRACT FROM AUTHOR]

Monomeric resin components from dental composites are toxic to fibroblasts in culture and thus may interfere with the local immune system of the pulp, reducing its effective defense potential, either by cytotoxicity or by a more specific immune mechanism. Therefore, the present study was undertaken to observe the cytotoxic effects elicited by certain unpolymerized components of resin composites upon the function of accessory pulp cells in mitogen-induced proliferation of T-lymphocytes. Accessory cells from the rat incisor pulp were released following enzymatic digestion with collagenase. The assay included incubation of these cells with purified T-lymphocytes from cervical lymph nodes for 72 h in the presence of different concentrations of the resin components. The proliferative T-lymphocyte response was monitored by ³H-thymidine incorporation. Initially, we conducted experiments on spleen cells to determine the proper concentration intervals for suitable testing of the resin components. To assess the individual susceptibility of accessory cells and T-lymphocytes, we pre-treated each of these cells with some of the test materials prior to assay. At low concentrations, urethane dimethacrylate (UDMA), bis-glycidyl methacrylate (bis-GMA), triethylene glycol dimethacrylate (TEGDMA), and bis-phenol A (BPA) increased spleen cell proliferation to concanavalin A (con A). Purified T-lymphocytes stimulated by pulpal cells did not show enhanced responses to UDMA, bis-GMA, glycidyl methacrylate (GMA), or N,N-dihydroxyethyl-p-toluidine (DHEpT). At higher concentrations, all substances except camphoroquinone (CAMP) showed inhibitory effects in both test systems. The in vitro study shows that resin components can evoke either immunosuppression or immunostimulation on mitogen-driven proliferation of purified T-lymphocytes and spleen cells. [ABSTRACT FROM AUTHOR]