共查询到20条相似文献,搜索用时 15 毫秒
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Diana C. Ynez Hemant Sahni Susan Ross Anisha Solanki Ching‐In Lau Eleftheria Papaioannou Alessandro Barbarulo Rebecca Powell Ulrike C. Lange David J. Adams Martino Barenco Masahiro Ono Fulvio D'Acquisto Anna L. Furmanski Tessa Crompton 《European journal of immunology》2019,49(1):66-78
The interferon‐inducible transmembrane (Ifitm/Fragilis) genes encode homologous proteins that are induced by IFNs. Here, we show that IFITM proteins regulate murine CD4+ Th cell differentiation. Ifitm2 and Ifitm3 are expressed in wild‐type (WT) CD4+ T cells. On activation, Ifitm3 was downregulated and Ifitm2 was upregulated. Resting Ifitm‐family‐deficient CD4+ T cells had higher expression of Th1‐associated genes than WT and purified naive Ifitm‐family‐deficient CD4+ T cells differentiated more efficiently to Th1, whereas Th2 differentiation was inhibited. Ifitm‐family‐deficient mice, but not Ifitm3‐deficient mice, were less susceptible than WT to induction of allergic airways disease, with a weaker Th2 response and less severe disease and lower Il4 but higher Ifng expression and IL‐27 secretion. Thus, the Ifitm family is important in adaptive immunity, influencing Th1/Th2 polarization, and Th2 immunopathology. 相似文献
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Niemeyer M Darmoise A Mollenkopf HJ Hahnke K Hurwitz R Besra GS Schaible UE Kaufmann SH 《Immunology》2008,123(1):45-56
Natural killer T (NKT) cells constitute a distinct lymphocyte lineage at the interface between innate and adaptive immunity, yet their role in the immune response remains elusive. Whilst NKT cells share features with other conventional T lymphocytes, they are unique in their rapid, concomitant production of T helper type 1 (Th1) and Th2 cytokines upon T-cell receptor (TCR) ligation. In order to characterize the gene expression of NKT cells, we performed comparative microarray analyses of murine resting NKT cells, natural killer (NK) cells and naïve conventional CD4+ T helper (Th) and regulatory T cells (Treg). We then compared the gene expression profiles of resting and alpha-galactosylceramide (αGalCer)-activated NKT cells to elucidate the gene expression signature upon activation. We describe here profound differences in gene expression among the various cell types and the identification of a unique NKT cell gene expression profile. In addition to known NKT cell-specific markers, many genes were expressed in NKT cells that had not been attributed to this population before. NKT cells share features not only with Th1 and Th2 cells but also with Th17 cells. Our data provide new insights into the functional competence of NKT cells which will facilitate a better understanding of their versatile role during immune responses. 相似文献
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Antigen presentation by macrophages is enhanced by the uptake of necrotic, but not apoptotic, cells 总被引:8,自引:0,他引:8
Barker RN Erwig LP Hill KS Devine A Pearce WP Rees AJ 《Clinical and experimental immunology》2002,127(2):220-225
The aim of this study was to determine whether phagocytosis of necrotic or apoptotic cells affects antigen presentation by murine bone marrow-derived macrophages. After uptake of necrotic neutrophils, macrophages were able to stimulate significantly higher T cell proliferation in vitro against both the recall antigen albumin and the mitogen concanavalin A. No such effect was seen following phagocytosis of apoptotic neutrophils. Flow cytometry revealed that, within 4h of ingestion, macrophages that had taken up the necrotic cells expressed higher levels of CD40 than those that had phagocytosed apoptotic cells. Macrophage cultures pulsed with apoptotic, but not necrotic, neutrophils contained higher levels of transforming growth factor beta1, but lower concentrations of tumour necrosis factor alpha, compared to untreated controls. Our interpretation of these results is that macrophages that have taken up necrotic neutrophils co-stimulate T cells with greater efficiency due to rapid CD40 up-regulation, whereas those that have ingested apoptotic cells are not only ineffective in co-stimulation, but also secrete inhibitory cytokine. 相似文献
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Askenase PW 《Clinical and experimental immunology》2001,125(3):345-350
Transfer of contact sensitivity (CS) responses by immune lymphoid cells was the first finding that distinguished cellular from humoral immunity. CS has remained the most studied T cell reaction in vivo, and is the prototype for a variety of delayed-type hypersensitivity (DTH) responses. DTH in essence is the recruitment of effector alphabeta-T cells out of vessels into peripheral tissues. The T cells then are activated by antigen presenting cells to produce pro-inflammatory cytokines. It has been assumed that the alphabeta-T cells alone are responsible, but recent studies show that three other lymphocyte subsets are involved: CS-inducing NK T cells, CS-initiating B-1 cells, and CS-assisting gammadelta-T cells. Therefore, the effector alphabeta-T cells are essential, but cannot be recruited into the tissues without the local action of IgM antibodies produced by B-1 cells rapidly (1 day) post-immunization. The IgM complexes with the challenge antigen to locally activate complement to lead to vascular activation required for T cell recruitment. This process occurs early (1-2 hours) in the elicitation phase, and is called CS-initiation. The essential CS-inducing NK T cells activate the B-1 cells by producing IL-4 rapidly (1 hour) after immunization, and gammadelta-T cells assist the local inflammatory function of the recruited CS-effector alphabeta-T cells. Thus, four lymphocyte subsets are required for elicitation of responses: CS-inducing NK T cells, CS-initiating B-1 cells, CS-assisting gammadelta-T cells, and finally the CS-effector alphabeta-T cells. Three of these four cell types are present in the immune lymphoid cell population that adoptively transfers CS: B-1 cells, gammadelta-T cells, and the alphabeta-T cells. 相似文献
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Interleukin-23 (IL-23) plays an essential role in driving intestinal pathology in experimental models of both T-cell-dependent and innate colitis. Furthermore, genome-wide association studies have identified several single-nucleotide polymorphisms in the IL-23 receptor (IL-23R) gene that are associated with either susceptibility or resistance to inflammatory bowel disease in humans. Although initially found to support the expansion and maintenance of CD4(+) T helper 17 (Th17) cells, IL-23 is now recognized as having multiple effects on the immune response, including restraining Foxp3(+) regulatory T-cell activity and inducing the expression of Th17-type cytokines from non-T-cell sources. Here we focus on Th17 cells and their associated cytokines IL-17A, IL-17F, IL-21 and IL-22. We review studies performed in mouse models of colitis where these effector cytokines have been shown to have either a pathogenic or a tissue-protective function. We also discuss the heterogeneity found within the Th17 population and the phenomenon of plasticity of Th17 cells, in particular the ability of these lymphocytes to extinguish IL-17 expression and turn on interferon-γ production to become Th1-like 'ex-Th17' cells. Interleukin-23 has been identified as a key driver in this process, and this may be an additional mechanism by which IL-23 promotes pathology in the intestinal tract. These 'ex-Th17' cells may contribute to disease pathogenesis through their secretion of pro-inflammatory mediators. 相似文献
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Iizuka A Ikarashi Y Yoshida M Heike Y Takeda K Quinn G Wakasugi H Kitagawa M Takaue Y 《Immunology》2008,123(1):100-107
CD1d-restricted natural killer T (NKT) cells can rapidly produce T helper type 1 (Th1) and Th2 cytokines and also play regulatory or pathological roles in immune responses. NKT cells are able to expand when cultured with alpha-galactosylceramide (alpha-GalCer) and interleukin (IL)-2 in a CD1d-restricted manner. However, the expansion ratio of human NKT cells is variable from sample to sample. In this study, we sought to determine what factor or factors are responsible for efficient in vitro expansion of NKT cells from various inbred mouse strains. Although the proportion of NKT cells in the spleen was nearly identical in each mouse strain, the growth rates of NKT cells cultured in vitro with alpha-GalCer and IL-2 were highly variable. NKT cells from the B6C3F1 and BDF1 mouse strains expanded more than 20-fold after 4 days in culture. In contrast, NKT cells from the strain C3H/HeN did not proliferate at all. We found that cell expansion efficiency correlated with the level of IL-4 detectable in the supernatant after culture. Furthermore, we found that exogenous IL-4 augmented NKT cell proliferation early in the culture period, whereas interferon (IFN)-gamma tended to inhibit NKT cell proliferation. Thus, the ratio of production of IL-4 and IFN-gamma was important for NKT cell expansion but the absolute levels of these cytokines did not affect expansion. This finding suggests that effective expansion of NKT cells requires Th2-biased culture conditions. 相似文献
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RIP2 contributes to Nod signaling but is not essential for T cell proliferation, T helper differentiation or TLR responses 总被引:1,自引:0,他引:1
Hall HT Wilhelm MT Saibil SD Mak TW Flavell RA Ohashi PS 《European journal of immunology》2008,38(1):64-72
Receptor-interacting protein 2 (RIP2), also known as CARDIAK and RICK, has been reported to play a role in both adaptive T cell responses and innate immunity as a mediator in TLR signaling and nucleotide-binding oligomerization domain (Nod) signaling. Because initial reports remain controversial, we have further examined both innate and adaptive immune responses in RIP2-deficient mice on the C57BL/6 background. Despite the up-regulation of RIP2 after T cell activation, we could not detect any defect in T cell proliferation or Th1/Th2 responses in RIP2-KO mice. Furthermore, we found that TLR responses in RIP2-deficient macrophages were normal. However, our analysis showed that Nod signaling was impaired in macrophages from RIP2-deficient mice. In conclusion, our data demonstrate a critical role for RIP2 in Nod signaling, while T cell proliferation, T helper differentiation and TLR responses were unaffected by the absence of RIP2. 相似文献
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Limited studies have addressed the ability of gammadelta T cells to become memory populations. We previously demonstrated that WC1.1(+) gammadelta T cells from ruminants vaccinated with killed Leptospira borgpetersenii proliferate and produce IFN-gamma in recall responses. Here we show that this response is dependent upon antigen-responsive CD4 T cells, at least across transwell membranes; this requirement cannot be replaced by IL-2. The response was also dependent upon in vivo priming, since gammadelta T cells from leptospira vaccine-naive animals did not respond to antigen even when co-cultured across membranes from antigen-responsive PBMC. Gammadelta T cells were the major antigen-responding T cell population for the first 4 wks following vaccination and replicated more rapidly than CD4 T cells. Primed WC1(+) gammadelta T cells circulated as CD62L(hi)/CD45RO(int)/CD44(lo), characteristics of T(CM) cells. When stimulated with antigen, they decreased CD62L, increased CD44 and CD25, and had no change in CD45RO expression. These changes paralleled those of the leptospira antigen-responsive CD4 T cells but differed from those of gammadelta T cells proliferating to mitogen stimulation. This system for in vivo gammadelta T cell priming is unique, since it relies on a killed antigen to induce memory and may be pertinent to designing vaccines that require type 1 pro-inflammatory cytokines. 相似文献