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The paper reviews the literature reports on low molecular weight (LMW) sensitizers that are commonly encountered in the work environment as well as on the major mechanisms responsible for their effect on the immune cells of the respiratory tract. Current studies have focused on: LMW-antigens; the role of airway epithelial and dendritic cells (DCs); activation of naive helper T (Th) cells by DCs; naive B cell-effector Th2 cell interactions; and activation of mast cells by LMW asthmogens. A better understanding of the pathogenesis of occupational asthma due to LMW asthmogens should facilitate the development of better diagnostics and the improvement of strategies for disease surveillance and intervention. [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]

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]

The oncofoetal antigen 5T4 is a promising T cell target in the context of colorectal cancer, as demonstrated by a recent clinical study where 5T4-specific T cell responses, induced by vaccination or cyclophosphamide, were associated with a significantly prolonged survival of patients with metastatic disease. Whilst Th1-type (IFN-γ+) responses specific to 5T4, and other oncofoetal antigens, are often readily detectable in early stage CRC patients and healthy donors, their activity is suppressed as the cancer progresses by CD4+CD25hiFoxp3+ regulatory T cells (Treg) which contribute to the immunosuppressive environment conducive to tumour growth. This study mapped the fine specificity of Th1 and Treg cell responses to the 5T4 protein. Surprisingly, both immunogenic peptides and those recognised by Tregs clustered in the same HLA-DR transcending epitope-rich hotspots within the 5T4 protein. Similarly, regions of low Th1-cell immunogenicity also did not contain peptides capable of stimulating Tregs, further supporting the notion that Treg and Th1 cells recognise the same peptides. Understanding the rules which govern the balance of Th1 and Treg cells responding to a given peptide specificity is, therefore, of fundamental importance to designing strategies for manipulating the balance in favour of Th1 cells, and thus the most effective anti-cancer T cell responses. [ABSTRACT FROM AUTHOR]

Summary: Pneumococcal infections cause a large global health burden, and the search for serotype‐independent vaccines continues. Existing conjugate vaccines reduce nasopharyngeal colonization by target serotypes. Such mucosal effects of novel antigens may similarly be important. CD4+ Th17 cell‐dependent, antibody‐independent reductions in colonization and enhanced clearance have been described in mice. Here we describe the evaluation of T helper type 17 (Th17) cytokine responses to candidate pneumococcal protein vaccine antigens in human cell culture, using adenoidal and peripheral blood mononuclear cells. Optimal detection of interleukin (IL)‐17A was at day 7, and of IL‐22 at day 11, in these primary cell cultures. Removal of CD45RO+ memory T cells abolished these responses. Age‐associated increases in magnitude of responses were evident for IL‐17A, but not IL‐22, in adenoidal cells. There was a strong correlation between individual IL‐17A and IL‐22 responses after pneumococcal antigen stimulation (P < 0·015). Intracellular cytokine staining following phorbol myristate acetate (PMA)/ionomycin stimulation demonstrated that  > 30% CD4+ T cells positive for IL‐22 express the innate markers γδT cell receptor and/or CD56, with much lower proportions for IL‐17A+ cells (P < 0·001). Responses to several vaccine candidate antigens were observed but were consistently absent, particularly in blood, to PhtD (P < 0·0001), an antigen recently shown not to impact colonization in a clinical trial of a PhtD‐containing conjugate vaccine in infants. The data presented and approach discussed have the potential to assist in the identification of novel vaccine antigens aimed at reducing pneumococcal carriage and transmission, thus improving the design of empirical clinical trials. [ABSTRACT FROM AUTHOR]

Background: Patients with metastatic sarcomas have poor outcomes and although the disease may be amenable to immunotherapies, information regarding the immunologic profiles of soft tissue sarcoma (STS) subtypes is limited.Methods: The authors identified patients with the common STS subtypes: leiomyosarcoma, undifferentiated pleomorphic sarcoma (UPS), synovial sarcoma (SS), well-differentiated/dedifferentiated liposarcoma, and myxoid/round cell liposarcoma. Gene expression, immunohistochemistry for programmed cell death protein (PD-1) and programmed death-ligand 1 (PD-L1), and T-cell receptor Vβ gene sequencing were performed on formalin-fixed, paraffin-embedded tumors from 81 patients. Differences in liposarcoma subsets also were evaluated.Results: UPS and leiomyosarcoma had high expression levels of genes related to antigen presentation and T-cell infiltration. UPS were found to have higher levels of PD-L1 (P≤.001) and PD-1 (P≤.05) on immunohistochemistry and had the highest T-cell infiltration based on T-cell receptor sequencing, significantly more than SS, which had the lowest (P≤.05). T-cell infiltrates in UPS also were more oligoclonal compared with SS and liposarcoma (P≤.05). A model adjusted for STS histologic subtype found that for all sarcomas, T-cell infiltration and clonality were highly correlated with PD-1 and PD-L1 expression levels (P≤.01).Conclusions: In the current study, the authors provide the most detailed overview of the immune microenvironment in sarcoma subtypes to date. UPS, which is a more highly mutated STS subtype, provokes a substantial immune response, suggesting that it may be well suited to treatment with immune checkpoint inhibitors. The SS and liposarcoma subsets are less mutated but do express immunogenic self-antigens, and therefore strategies to improve antigen presentation and T-cell infiltration may allow for successful immunotherapy in patients with these diagnoses. Cancer 2017;123:3291-304. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. [ABSTRACT FROM AUTHOR]

Background: Liver fibrosis which mainly occurs upon chronic hepatitis virus infection potentially leads to portal hypertension, hepatic failure and hepatocellular carcinoma. However, the immune status of Th17 and Treg cells in liver fibrosis is controversial and the exact mechanisms remain largely elusive.Methods: Liver tissues and peripheral blood were obtained simultaneously from 32 hepatitis B virus infected patients undergoing surgery for hepatocellular carcinoma at the medical center of Sun Yat-sen University. Liver tissues at least 3 cm away from the tumor site were used for the analyses. Levels of Th17 cells and regulatory T cells were detected by flow cytometry analysis and immunohistochemistry. In vitro experiment, we adopted magnetic cell sorting to investigate how hepatic stellate cells regulate the levels of Th17 cells and regulatory T cells.Results: We found that hepatic Th17 cells and regulatory T cells were increased in patients with advanced stage HBV-related liver fibrosis. Hepatic stellate cells upregulated the levels of Th17 cells and regulatory T cells via PGE2/EP2 and EP4 pathway.Conclusions: We found that the increased levels of Th17 cells and regulatory T cells were upregulated by hepatic stellate cells. These results may provide insight into the role of hepatic stellate cells and Th17 cells and regulatory T cells in the persistence of fibrosis and into the occurrence of hepatocellular carcinoma following cirrhosis. [ABSTRACT FROM AUTHOR]

Regulatory T cells (Treg) play an important role in fetal protection. They expand during normal pregnancy and protect fetal antigens from maternal effector cells. Their effect is associated with the up-regulation of tolerance-associated molecules at the fetal-maternal interface. Among these, Heme Oxygenase-1 (HO-1, coded by Hmox1) is of special importance as its blockage correlates with increased abortion rates and its up-regulation positively affects pregnancy outcome. Here, we aimed to investigate whether the protective effect of Treg is mediated by HO-1 in a mouse model. HO-1 blockage by Zinc Protoporhyrin (ZnPPIX) abrogated the protective effect of Treg transfer. We found that HO-1 is important in maintaining maternal dendritic cells (DCs) in an immature state, which contributes to the expansion of the peripheral Treg population. This brings to light one essential pathway through which Treg mediates the semi- allogeneic fetus tolerance. [ABSTRACT FROM AUTHOR]

We have previously demonstrated that antigens chemically coupled to the surface of liposomes consisting of unsaturated fatty acids were cross-presented by antigen-presenting cells (APCs) to CD8+T cells, and that this process resulted in the induction of antigen-specific cytotoxic T lymphocytes. In the present study, the mechanism by which the liposome-coupled antigens were cross-presented to CD8+ T cells by APCs was investigated. Confocal laser scanning microscopic analysis demonstrated that antigens coupled to the surface of unsaturated-fatty-acid-based liposomes received processing at both MHC class I and class II compartments, while most of the antigens coupled to the surface of saturated-fatty-acid-based liposomes received processing at the class II compartment. In addition, flow cytometric analysis demonstrated that antigens coupled to the surface of unsaturated-fatty-acid-liposomes were taken up by APCs even in a 4°C environment; this was not true of saturated-fatty-acid-liposomes. When two kinds of inhibitors, dimethylamiloride (DMA) and cytochalasin B, which inhibit pinocytosis and phagocytosis by APCs, respectively, were added to the culture of APCs prior to the antigen pulse, DMA but not cytochalasin B significantly reduced uptake of liposome-coupled antigens. Further analysis of intracellular trafficking of liposomal antigens using confocal laser scanning microscopy revealed that a portion of liposome-coupled antigens taken up by APCs were delivered to the lysosome compartment. In agreement with the reduction of antigen uptake by APCs, antigen presentation by APCs was significantly inhibited by DMA, and resulted in the reduction of IFN-γ production by antigen-specific CD8+T cells. These results suggest that antigens coupled to the surface of liposomes consisting of unsaturated fatty acids might be pinocytosed by APCs, loaded onto the class I MHC processing pathway, and presented to CD8+T cells. Thus, these liposome-coupled antigens are expected to be applicable for the development of vaccines that induce cellular immunity. [ABSTRACT FROM AUTHOR]

Objectives: Successful engraftment of human T-lymphotropic virus type 1 (HTLV-1)-infected cells and a marked increase of proviral DNA loads (PVLs) in non-obese diabetic/severe combined immunodeficient (NOD/SCID)/γcnull (NOG) mice have been reported. Whether the increased PVL in transplanted mice is due to the new infection of HTLV-1 was examined. Methods: Mononuclear cells from 3 NOG mice with primary engraftment from asymptomatic HTLV-1 carriers were transplanted into a second group of NOG mice. HTLV-1 PVL, proviral integration by fluorescence in situ hybridization assay, expression of viral antigen, and T-cell clonality were analyzed. Results: The PVLs in the secondarily transplanted NOG mice were significantly higher than those of primarily transplanted NOG mice. Multiple signals of HTLV-1 proviruses in the nucleus of the infected cells were revealed by fluorescence in situ hybridization analysis. Expression of HTLV-1 tax/rex mRNA and antigen was observed. The variety of T-cell clones was limited in the transplanted NOG mice. Conclusions: Multiple proviral integrations were considered to be due to the new infection from HTLV-1-infected cells to the other cells. Only a certain fraction of T cells seemed to have selectively survived in NOG mice after engraftment. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Deals with a research which revealed that human γδ T cells can join dendritric cells in the professional antigen-presenting cell club. Difference between γδ T cells from αβ T cells; Effects if T-cell receptor triggering on γδ T cells in human peripheral blood; Potential role for Vδ2+ T cells in antigen presentation to αβ T cells.

Bacterial capsular polysaccharides (PS) which naturally contain zwitterionic charge motifs (ZPS) possess specific immunostimulatory activity, leading to direct activation of antigen-presenting cells (APCs) through Toll-like receptor 2 (TLR2) and of T cells in co-culture systems. When administered intraperitoneally, ZPS and bacteria expressing them are involved in the induction or regulation of T-cell dependent inflammatory processes such as intra-abdominal abscess formation. To generate vaccine candidates with antigen and adjuvant properties in one molecule we have chemically introduced zwitterionic motifs into naturally anionic PS and find that the resulting ZPS are TLR2 agonists, able to activate human and mouse APCs. Since T-regulatory cells and other T-cell subsets express TLR2, and TLR2 engagement modifies functionality and activation state of these cells, we speculate that most effects induced by natural and chemically derived ZPS may be explained by their TLR2 agonist properties, presumably through the combined action on TLR2-expressing APCs and T cells. [ABSTRACT FROM AUTHOR]

Why is it that T cells are blind to antigens in solution but highly sensitive to antigens anchored on a surface? The authors show that this is not due to antigen clustering, but could involve mechanical forces associated with cell locomotion. [ABSTRACT FROM AUTHOR]

The ability to develop and sustain populations of memory T cells after infection or immunization is a hallmark of the adaptive immune response and a basis for protective vaccination against infectious disease. Technical advances that allow direct ex vivo identification and characterization of antigen-specific CD8+ T cells at various stages of the response to infection or vaccination in mouse models have fuelled efforts to characterize the factors that control memory CD8+ T-cell generation. Here, we dissect the input signals that shape the characteristics of the memory CD8+ T-cell response and discuss how manipulation of these signals has the potential to reshape CD8+ T-cell memory and improve the efficacy of vaccination. [ABSTRACT FROM AUTHOR]

Background: The lung is divided into two major compartments: the alveolar space and the parenchyma. The alveolar macrophages are the first line of leukocytes in the lung taking up incoming microbes or microbial antigens whereas the parenchymal dendritic cells (DCs) are believed to be the sole potent antigen presenting cells (APCs) in the lung. Both resting alveolar macrophages and parenchymal DCs express CD11c. Several important questions remain to be elucidated: 1] to which extent the alveolar space and lung parenchymal CD11c+ APCs differ in their phenotype and ability to activate naïve T cells; 2] whether they differ in their ability to activate antigen-experienced or -primed T cells; and 3] whether these lung CD11c+ APC populations differ from the splenic CD11c+ APCs which have been commonly used for understanding APC biology. Results: CD11c+ APCs from the alveolar space, lung parenchyma, and the spleen display differential co-stimulatory molecule expression and cytokine responsiveness upon stimulation. Alveolar space APCs are weak activators of naïve T cells compared to lung parenchymal and splenic CD11c+ APC populations. However, alveolar space APCs are able to potently activate the in vivo microbial antigen-primed T cells to a similar extent as lung parenchymal and splenic APCs. Conclusion: Together our findings indicate that alveolar CD11c+ APCs have a specialized T cell-activating function, capable of activating antigen-primed, but not naïve, T cells whereas lung CD11c+ APCs are capable of activating both the naïve and antigen-primed T cell populations. [ABSTRACT FROM AUTHOR]

Background: CD4+CD25high regulatory T (TReg) cells modulate antigen-specific T cell responses, and can suppress anti-viral immunity. In HTLV-1 infection, a selective decrease in the function of TReg cell mediated HTLV-1-tax inhibition of FOXP3 expression has been described. The purpose of this study was to assess the frequency and phenotype of TReg cells in HTLV-1 asymptomatic carriers and in HTLV-1-associated neurological disease (HAM/TSP) patients, and to correlate with measures of T cell activation. Results: We were able to confirm that HTLV-I drives activation, spontaneous IFNγ production, and proliferation of CD4+ T cells. We also observed a significantly lower proportion of CTLA-4+ TReg cells (CD4+CD25high T cells) in subjects with HAM/TSP patients compared to healthy controls. Ki-67 expression was negatively correlated to the frequency of CTLA-4+ TReg cells in HAM/TSP only, although Ki-67 expression was inversely correlated with the percentage of CD127low TReg cells in healthy control subjects. Finally, the proportion of CD127low TReg cells correlated inversely with HTLV-1 proviral load. Conclusion: Taken together, the results suggest that TReg cells may be subverted in HAM/TSP patients, which could explain the marked cellular activation, spontaneous cytokine production, and proliferation of CD4+ T cells, in particular those expressing the CD25highCD127low phenotype. TReg cells represent a potential target for therapeutic intervention for patients with HTLV-1-related neurological diseases. [ABSTRACT FROM AUTHOR]

Background: Cellular immunity plays a crucial role in cytomegalovirus (CMV) infection and substantial populations of CMV-specific T cells accumulate throughout life. However, although CMV infection occurs during childhood, relatively little is know about the typical quantity and quality of T cell responses in pediatric populations. Methods: One thousand and thirty-six people (Male/Female = 594/442, Age: 0-19 yr.; 959 subjects, 20-29 yr.; 77 subjects) were examined for HLA typing. All of 1036 subjects were tested for HLA-A2 antigen. Of 1036 subjects, 887 were also tested for HLA-A23, 24 antigens. In addition, 50 elderly people (Male/Female = 11/39, Age: 60-92 yr.) were also tested for HLA-A2 antigen. We analyzed the CD8+ T cell responses to CMV, comparing these to responses in children and young. The frequencies, phenotype and function CD8+ T cells for two imunodominant epitopes from pp65 were measured. Results: We observed consistently high frequency and phenotypically "mature" (CD27 low, CD28 low, CD45RA+) CMV-specific CD8+ T cell responses in children, including those studied in the first year of life. These CD8+ T cells retained functionality across all age groups, and showed evidence of memory "inflation" only in later adult life. Conclusion: CMV consistently elicits a very strong CD8+ T cell response in infants and large pools of CMV specific CD8+ T cells are maintained throughout childhood. The presence of CMV may considerably mould the CD8+ T cell compartment over time, but the relative frequencies of CMV-specific cells do not show the evidence of a population-level increase during childhood and adulthood. This contrast with the marked expansion ("inflation") of such CD8+ T cells in older adults. This study indicates that large scale analysis of peptide specific T cell responses in infants is readily possible. The robust nature of the responses observed suggests vaccine strategies aimed at priming and boosting CD8+ T cells against major pathogens (including HIV, malaria and CMV itself) could be successful in this age-group. [ABSTRACT FROM AUTHOR]

Peptide antigens are presented to T cells by major histocompatibility complex (MHC) molecules, with endogenous peptides presented by MHC class I and exogenous peptides presented by MHC class II. In contrast to the MHC system, CD1 molecules bind lipid antigens that are presented at the antigen-presenting cell (APC) surface to lipid antigen-reactive T cells. Because CD1 molecules survey endocytic compartments, it is self-evident that they encounter antigens from extracellular sources. However, the mechanisms of exogenous lipid antigen delivery to CD1-antigen-loading compartments are not known. Serum apolipoproteins are mediators of extracellular lipid transport for metabolic needs. Here we define the pathways mediating markedly efficient exogenous lipid antigen delivery by apolipoproteins to achieve T-cell activation. Apolipoprotein E binds lipid antigens and delivers them by receptor-mediated uptake into endosomal compartments containing CD1 in APCs. Apolipoprotein E mediates the presentation of serum-borne lipid antigens and can be secreted by APCs as a mechanism to survey the local environment to capture antigens or to transfer microbial lipids from infected cells to bystander APCs. Thus, the immune system has co-opted a component of lipid metabolism to develop immunological responses to lipid antigens. [ABSTRACT FROM AUTHOR]

Lohse L, Nielsen J, Kamstrup S, Oleksiewicz MB, Eriksen L. Porcine humoral immune responses to multiple injections of murine monoclonal antibodies. APMIS 2005;113:489–96. In humans and cattle, multiple injections of murine monoclonal antibodies (m-mAbs) induce anti-mouse antibody responses. The objectives of the present study were to investigate whether a similar response could be seen when pigs were subjected to m-mAb therapy, and to study the kinetics of such a response. In two separate animal experiments, long-term treatment was performed with m-mAbs at low-dose levels and therapeutic levels, respectively. Two specific m-mAbs that recognized cognate antigen in the pigs (CD4 and CD8 surface antigens on T-lymphocytes) and two irrelevant control m-mAbs having no cognate antigen in the pigs were used. Enzyme-linked immunosorbent assays (ELISA) were used to quantitate the circulating m-mAbs, as well as the induced pig anti-mouse antibodies (PAMA), in serum samples from m-mAb-treated pigs. As expected, we generally saw vigorous PAMA responses within 10 days after the start of m-mAb treatment with the specific m-mAbs. However, the different mAbs showed striking differences in the kinetics and levels of PAMA responses, differences that might be ascribed to the m-mAb formulation and epitope specificity. In conclusion, treatment of pigs with m-mAbs against T-cell surface antigens induced rapid PAMA responses. This may influence and possibly decrease the effect of the m-mAb treatment by narrowing the time period where m-mAbs can efficiently be used for cell depletion. [ABSTRACT FROM AUTHOR]

Discusses two studies which characterized a gated channel into the proteasome core particle. Reference to the studies published in "Nature Structural Biology and Nature" journal; Structure of the 20S proteasome; Information on how the 11S particle opens the proteasome's gate; Role of proteasome in antigens for presentation to T cells.

Recent years have seen so-called natural killer T (NKT) cells emerge as important regulators of the immune response. The existence of NKT-cell subsets, and other types of T cell that resemble NKT cells, is an ongoing source of confusion in the literature. This perspective article seeks to clarify which cells fall under the NKT-cell umbrella, and which might be best considered as separate. [ABSTRACT FROM AUTHOR]

Background/Aims: The antigen phenotype of human osteoblast-like cells suggests that they are related to other cellular populations and may also have immunologic functions in common. Methods: Flow cytometry and transmission electron microscopy were used to show the phagocytotic activity of osteoblast-like cells in culture. The allogeneic stimulation of T cells by human osteoblast-like cells was determined by the measurement of T cell proliferation. Results: We demonstrated in vitro that human osteoblast-like cells isolated from normal bone specimens obtained during mandibular osteotomy can phagocytose particles of different nature and size and can stimulate allogeneic T cells. Phagocytosis of microorganisms (E.coli, Klebsiella or C. albicans) was observed, although at a very low rate of activity in comparison with the phagocytosis of latex particles. Conclusion: Our results suggest that human osteoblast-like cells may perform immunologic functions and act as antigen presentation cells. [ABSTRACT FROM AUTHOR]

Many studies have shown the central importance of the co-receptors CD28, inducible costimulatory molecule (ICOS) and cytotoxic T lymphocyte antigen 4 (CTLA4) in the regulation of many aspects of T-cell function. CD28 and ICOS have both overlapping and distinct functions in the positive regulation of T-cell responses, whereas CTLA4 negatively regulates the response. The signalling pathways that underlie the function of each of the co-receptors indicate their shared and unique properties and provide compelling hints of functions that are as yet uncovered. Here, we outline the shared and distinct signalling events that are associated with each of the co-receptors and provide unifying concepts that are related to signalling functions of these co-receptors. [ABSTRACT FROM AUTHOR]

Each of the human CD1 proteins takes a different route through secretory and endocytic compartments before finally arriving at the cell surface, where these proteins present glycolipid antigens to T cells. Recent studies have shown that adaptor-protein complexes and CD1-associated chaperones control not only CD1 trafficking, but also the development and activation of CD1-restricted T cells. This indicates that CD1 proteins, similar to MHC class I and II molecules, selectively acquire certain antigens in distinct cellular subcompartments. Here, we summarize evidence supporting the hypothesis that CD1 proteins use separate, but parallel, pathways to survey endosomal compartments differentially for lipid antigens. [ABSTRACT FROM AUTHOR]

Cell types in a human experimental gingivitis model were analyzed sequentially on days 0, 4, 8, and 21 of a no oral hygiene period. The cells were characterized using enzyme and surface antigen markers. In all but two of the day 0 specimens a small inflammatory infiltrate was localized immediately beneath the junctional epithelium. These, essentially lymphocytic lesions, consisted of over 70% T-cells as suggested by the phenotype T-enzyme +ve/T-cell surface antigen +ve/B-cell surface antigen -ve/HLA-DR-ve/B-cell subset antigen -ve. At days 4,8, and 21, although the size of the infiltrate increased, its essential nature did not change. At all times the majority of lymphocytes (over 70%) had the characteristic T-cell phenotype. These results show that in the developing gingival lesion in humans a T-cell dominated lesion occurs and persists at least for the 3 week experimental period used in the present study. [ABSTRACT FROM AUTHOR]

T cells from patients with CVID have defects that may relate to the failure in vivo of B cell production of antibodies. Antigen-driven responses of T cells from CVID patients and normal subjects have been assessed by measuring DNA synthesis in vitro. Low density cells enriched for antigen-presenting dendritic cells were pulsed with purified protein derivative (PPD) and cultured with autologous T cells. Overall, T cells from CVID patients showed a significantly low mean response to PPD, although non-specific DNA synthesis induced in CVID T cells by IL-2 was within the normal range. However, mean PPD-specific T cell responses in CVID were not restored by IL-2 irrespective of the presence of monocytes. Depletion of CD8+ cells also failed to restore the mean PPD response of CVID CD4+ T cells. Limiting dilution analysis showed that in CVID there was a reduced frequency of antigen-specific cells within the T cell preparations. The mean frequency of the PPD-specific T cells in cultures from patients vaccinated with bacille Calmette Guérin (BCG) was reduced to 1 in 109000 T cells compared with 1 in 18600 T cells in BCG-vaccinated normal donors. These data show that the reduced PPD-specific response in CVID is due to a partial peripheral loss of antigen-specific cells. [ABSTRACT FROM AUTHOR]

Purified human mononuclear cell subpopulations have been evaluated in the in vitro lymphocyte proliferation assay. Monocyte-depleted mononuclear cells had reduced or absent responses to mitogens and antigens which could be restored to the original mononuclear cell response by addition of purified plastic adherent cells. Purified T lymphocytes obtained by density gradient centrifugation of E-rosette-forming cells demonstrated low but significant proliferative responses to mitogens, but no significant response to antigens. The addition of monocytes potentiated the response of purified T cells to mitogens and antigens, but did not fully reconstitute the original mononuclear cell response unless non-T lymphocytes were also present. It is concluded that mononuclear cell proliferation represents a complex mechanism of cellular interaction involving multiple subpopulations of cells. [ABSTRACT FROM AUTHOR]

The evolution of cells of the monocyte-macrophage lineage (MML cells) in the spleen of Leishmania donovani (LD) infected BALB/c mice was studied. Spleen cells were fractionated on a discontinuous percoll gradient and adherent cells (AC) were purified from fractionated spleen cells by adherence steps that appeared at the interfaces of 25-35%, 35-40%, 40-45% and 45-50% percoll gradients. The AC were characterized as MML cells on the basis of positive staining for non-specific esterase. Adherent cells that appeared at the interfaces of 25-35% and 40-45% were defined as A and C, respectively, and both of them showed extreme variation in a progressive infection. It was observed that A supported parasite replication whereas C remained refractory when infected with LD in vitro. Furthermore, when A cells and C cells were used as antigen-presenting cells to stimulate mixed population of IFN-γ producing and IL-4 producing T-cells, it was observed that IL-4 and IFN-γ were the predominating cytokine in the T-cell supernatant, respectively. Both A and C were found to be increased hand-in-hand up to 5 months of infection and from then on A decreased and C increased in their numerical strength (A-C reciprocity). The evolution of A-C reciprocity coincided with the gradual reduction in the parasitaemia in the spleen suggesting that this may contribute to the acquisition of anti-leishmania immunity. [ABSTRACT FROM AUTHOR]

The role of suppressor cells in control of persistent infections may be of profound importance. Whether a positive immune response or suppression of immunity is generated at the time of initial exposure to pathogens causing such infections may in part be due to the nature of the initial antigen presentation to the specific cells of the immune system. We have shown that in vivo modulation of epidermal APCs by an environmentally encountered stimulus (UV-B light exposure) and subsequent transfer of these APCs together with live HSV-1 to naive syngeneic recipients is sufficient to generate suppression of DH rather than DH to HSV-1. This suppression is T-cell mediated and specific for HSV-l. The phenotype of the Ts cell induced by epidermal cell transfer is Thyl+ L3T4+ Ly2-. [ABSTRACT FROM AUTHOR]

The response of primed T cells to keyhole limpet haemocyanin (KLH) was used to compare the characteristics of antigen presentation by lymphoid dendritic cells, splenic and peritoneal macrophages. In a similar manner to macrophages, purified dendritic cells could be pulsed with antigen and subsequently fixed by brief glutaraldehyde fixation and still retain antigen presenting activity. Also, as previously reported for macrophages, presentation could be inhibited by chloroquine. These functional experiments suggested that the pathway of antigen presentation in dendritic cells and macrophages was similar or identical. However, biochemical studies, using radiolabelled antigen, showed that dendritic cells do not significantly degrade large proteins such as KLH to TCA-soluble form, but partially hydrolyse them to smaller peptide fragments. The significance of these results in terms of a model of the cellular pathways of antigen presentation is discussed. [ABSTRACT FROM AUTHOR]

A study has been made of the variables concerned in allotype suppression of adult spleen cells in the adoptive transfer system. These are: SRBC (antigen) dose; the dose and timing of injection of anti-allotype serum IgG; the number of spleen cells transferred and whether these cells were taken from primed or unprimed donors. Adoptively transferred primed cells are considerably less susceptible to suppression by concomitantly injected anti-allotype serum IgG than are unprimed spleen cells. Injection of anti-allotype serum during the period after adoptive transfer, has shown that primed cells loose their susceptibility sooner (2 days) than the unprimed cells (4 days). Allotype heterozygous CBA spleen cells arc less susceptible to allotype suppression than either allotypically homozygous or heterozygous non-H-2k cells (H-2b,d, or s). Allotype suppression of the TI IgG response to DNP-Ficoll was measured 7 days after adoptive transfer of allotype-homozygous cells from both normal and nude CBA mice (unprimed). The results indicate that T cells do not play a role in the initiation of short-term allotype suppression in the adoptive transfer system. [ABSTRACT FROM AUTHOR]

Monoclonal anti-HLA-DR antibodies inhibited the production of interleukin-2 (IL-2) when added from the initiation of autologous (AMLR) and allogeneic (MLR) mixed lymphocyte reactions, but not 60 h later. The inhibitory activity of the anti-DR sera became apparent 8 h after initiation of the cultures and was maintained throughout the culture period. Interleukin-1 (IL-1) added to cultures carried out in the absence of the anti-DR antibodies significantly enhanced the production of IL-2, whereas addition of IL-1 to anti-DR-treated AMLR and MLR cultures did not restore or increase the synthesis of IL-2. However, when the anti-DR antibodies were added to IL-1-supplemented AMLR and MLR cultures 60 h or more after initiation of the reactions, the antiserum no longer inhibited the capacity of I L-I to promote the synthesis of IL-2 or the production of IL-2. Finally, resting T cells were unresponsive to IL-1 and did not produce IL-2. It thus seemed that the anti-DR antibodies inhibited production of IL-2 in AMLR and MLR by rendering the IL-2 producer T cells unresponsive to IL-1. Cyclosporin-A, a drug that abrogates activation of T cells by blocking their receptors for HLA-DR antigens, also rendered IL-2-producer T cells unresponsive to IL-1 and abrogated the production of IL-2 in AMLR and MLR. Since resting T cells do not respond to IL-1 or produce IL-2, it is concluded that HLA-DR antigens of the stimulator cells participate in the production of IL-2 in AMLR and MLR by enabling the IL-2 producer T lymphocytes to respond to IL-1. Interleukin-1 promotes the production of IL-2 by IL-1-sensitive T cells. Once the IL-2-producer T cells become sensitive to IL-1, there is no further requirement for HLA-DR antigens. [ABSTRACT FROM AUTHOR]

Phytohaemagglutinin-induced human T-lymphocyte colony formation in semisolid agar culture is the property of erythrocyte rosette-forming cells (E-RFC) negative for the 7S IgG receptor (FcR-), E-RFC positive for the 7S IgG receptor (FcR-), on the other hand, exhibit a limited capacity for colony formation and suppress colonies formed by FcR- E-RFC. T colonies are composed of small lymphocytes and lymphoblasts, the vast majority being negative for the Fc receptor. Most colony cells (86%) carry the Leu 3a antigen, suggesting that they belong to the inducer/helper T-cell subset. FcR+ colony suppressor cells are small, slowly sedimenting cells (sedimentation velocity <3.8 mm/h) and are strongly adherent to plastic, and their activity depends on the ability to synthesize DNA. [ABSTRACT FROM AUTHOR]

The article reports on the study which focuses on Toxoplasma gondii tachyzoites that have infected host cells residing in the parasitophorous vacuole (PV). Researchers have generated a system which will permit them to trace antigen-specific T-cell responses to T. gondii-derived antigens espousing phagocytosis of infected cells or dead parasites. It reveals that T. gondii-derived antigens are cross-presented by major histocompatibility complex (MHC) class I molecules to CD8+ cells.

The article provides information on an immunological research involving the differentiation of T helper 17 cells. It is stated that a present study has indicated that CD40-CD40 ligand crosstalk is needed for the cell differentiation of Th 17 cells in vitro and in vivo. Data in the study has showed that strong antigenic and pathogenic stimuli worked together to drive Th 17-cell differentiation.

Isoglobotriaosylceramide (iGb3) is a stimulatory antigen for a unique type of T cell, Natural Killer T cells. Produced in the lysosomal compartment by mammalian antigen-presenting cells, iGb3 is one of the few clearly identified carbohydrate ligands for biological receptors. A major source of glycoconjugate structural diversity arises from the possibility of forming different linkages between the same monosaccharide units. Globotriaosylceramide (Gb3) exists as a natural isomer for iGb3, and both isomers are frequently found together in mixtures of glycosphingolipids extracted from mammalian cell membranes. Discriminating these isomers has been feasible using monoclonal antibodies raised against specific carbohydrate epitopes, or by unambiguous structural characterization, which requires relatively large amounts of pure compounds isolated from grams, or tens of grams, of biological samples. However, the precise detection of iGb3 from small amounts of biological samples, where it may be mixed with Gb3 present in much higher abundance, is a prerequisite for answering further important biological questions such as stimulation of NKT cells. Here we describe a specific and sensitive method based on ion trap mass spectrometry to discriminate iGb3 from Gb3. We also demonstrate its application to quantifying the amount of iGb3 in a prototype antigen-presenting cell, rat RBL-CD1d cells, using a chemically synthesized short N-acyl chain iGb3 as internal standard. This methodology may have wide implications for functional glycosphingolipidomics of immune cells and glycosphingolipid biomarker analysis. [ABSTRACT FROM AUTHOR]

The article discusses several studies that shed light on the exact location of primary CD8+ T-cell activation in lymph nodes and on memory CD8+ T-cell reactivation in peripheral tissues. It was found that infected cells can be seen in a continuous sheet below the lymph node sub-capsular sinus (SCS) within 2-3 hours of virus inoculation. The studies also showed that antigen encounter in peripheral tissues can result in the reactivation of memory CD8+ T-cells.

Focuses on the anti-bacterial effect of CD1a-restricted T cells specific for mycobacteria-infected cells. Molecular identity of CD1a-presented antigens; Difference between didehydroxymycobactin and mycobactin; Fatty acyl chains of lipopeptides.