1,721,103 research outputs found
TCR tuning of T cell subsets
No full textAfter selection in the thymus, the post-thymic T cell compartments comprise heterogenous subsets of naive and memory T cells that make continuous T cell receptor (TCR) contact with self-ligands bound to major histocompatibility complex (MHC) molecules. T cell recognition of self-MHC ligands elicits covert TCR signaling and is particularly important for controlling survival of naive T cells. Such tonic TCR signaling is tightly controlled and maintains the cells in a quiescent state to avoid autoimmunity. Here, we review how naive and memory T cells are differentially tuned and wired for TCR sensitivity to self and foreign ligands
© 2018 John Wiley & Sons A/S.2
Characterization of the compensatory neuroprotective mechanism against mitochondrial dysfunction in Parkinson’s disease
No full textParkinson’s disease, mitochondrial compensatory mechanism, TSPO, disease progression, 파킨슨병, 미토콘드리아 보상 기전, TSPO, 질병 진행DoctordCollectio
T Cell's Sense of Self: a Role of Self-Recognition in Shaping Functional Competence of Naïve T Cells
Full text linkPost-thymic naïve T cells constitute a key cellular arm of adaptive immunity, with a well-known characteristic of the specificity and robustness of responses to cognate foreign antigens which is presented as a form of antigen-derived peptides bound to major histocompatibility complex (MHC) molecules by antigen-presenting cells (APCs). In a steady state, however, these cells are resting, quiescent in their activity, but must keep full ranges of functional integrity to mount rapid and robust immunity to cope with various infectious pathogens at any time and space. Such unique property of resting naïve T cells is not acquired in a default manner but rather requires an active mechanism. Although our understanding of exactly how this process occurs and what factors are involved remains incomplete, a particular role of self-recognition by T cells has grown greatly in recent years. In this brief review, we discuss recent data on how the interaction of T cells with self-peptide MHC ligands regulates their functional responsiveness and propose that variable strength of self-reactivity imposes distinctly different levels of functional competence and heterogeneity. © 2017. The Korean Association of Immunologists
Differential responsiveness of innate-like IL-17- and IFN-γ- producing γδ T cells to homeostatic cytokines
No full textγδ T cells respond to molecules upregulated following infection or cellular stress using both TCR and non-TCR molecules. The importance of innate signals versus TCR ligation varies greatly. Both innate-like IL-17-producing γδ T (γδT-17) and IFN-g- producing γδ T (γδT-IFNg) subsets tune the sensitivity of their TCR following thymic development, allowing robust responses to inflammatory cytokines in the periphery. The remaining conventional γδ T cells retain high TCR responsiveness. We determined homeostatic mechanisms that govern these various subsets in the peripheral lymphoid tissues. We found that, although innate-like γδT-17 and γδT-IFNg cells share elements of thymic development, they diverge when it comes to homeostasis. Both exhibit acute sensitivity to cytokines compared with conventional γδ T cells, but they do not monopolize the same cytokine. γδT-17 cells rely exclusively on IL-7 for turnover and survival, aligning them with NKT17 cells; IL-7 ligation triggers proliferation, as well as promotes survival, upregulating Bcl-2 and Bcl-xL. γδT-IFNg cells instead depend heavily on IL-15. They display traits analogous to memory CD8+ T cells and upregulate Bcl-xL and Mcl-1 upon cytokine stimulation. The conventional γδ T cells display low sensitivity to cytokine-alone stimulation and favor IL-7 for their turnover, characteristics reminiscent of naive ab T cells, suggesting that they may also require tonic TCR signaling for population maintenance. These survival constraints suggest that γδ T cell subsets do not directly compete with each other for cytokines, but instead fall into resource niches with other functionally similar lymphocytes. © 2016 by The American Association of Immunologists, Inc
Copyright © 2016 by The American Association of Immunologists, Inc. All rights reserved.116161sciescopu
Intranasal immunization with pneumococcal surface protein A in the presence of nanoparticle forming polysorbitol transporter adjuvant induces protective immunity against the Streptococcus pneumoniae infection
No full textDeveloping effective mucosal subunit vaccine for the Streptococcus pneumoniae has been unsuccessful mainly because of their poor immunogenicity with insufficient memory T and B cell responses. We thus address whether such limitation can be overcome by introducing effective adjuvants that can enhance immunity and show here that polysorbitol transporter (PST) serves as a mucosal adjuvant for a subunit vaccine against the Streptococcus pneumoniae. Pneumococcal surface protein A (PspA) with PST adjuvant induced protective immunity against S. pneumoniae challenge, especially long-term T and B cell immune responses. Moreover, we found that the PST preferentially induced T helper (Th) responses toward Th2 or T follicular helper (Tfh) cells and, importantly, that the responses were mediated through antigen-presenting cells via activating a peroxisome proliferator-activated receptor gamma (PPAR-γ) pathway. Thus, these data indicate that PST can be used as an effective and safe mucosal vaccine adjuvant against S. pneumoniae infection. State of Significance: In this study, we suggested the nanoparticle forming adjuvant, PST works as an effective adjuvant for the pneumococcal vaccine, PspA. The PspA subunit vaccine together with PST adjuvant efficiently induced protective immunity, even in the long-term memory responses, against Streptococcus pneumoniae lethal challenge. We found that PspA with PST adjuvant induced dendritic cell activation followed by follicular helper T cell responses through PPAR-γ pathway resulting long-term memory antibody-producing cells. Consequently, in this paper, we suggest the mechanism for safe nanoparticle forming subunit vaccine adjuvant against pneumococcal infection. © 2019 Acta Materialia In
Unique Features of Naive CD8+ T Cell Activation by IL-2
No full textIL-2 has a pervasive influence on the immune system and dictates the survival and differentiation of multiple T cell subsets, including
CD4 regulatory T cells, CD4 Th cells, and CD8 memory cells. IL-2 is synthesized by T cells during the early stages of the
immune response and promotes T cell expansion and effector cell generation after initial activation via TCR signaling. Based on
studies with activated T cell lines maintained in vitro, IL-2 is known to activate multiple signaling pathways that show considerable
overlap with the pathways elicited via the TCR. In this paper, we have examined IL-2 signaling under TCR-independent conditions,
namely by culturing purified resting naive CD8 T cells with IL-2 in the absence of Ag or APC. Under these conditions, we show in
this study that IL-2 elicits a unique pattern of signaling associated with strong lymphocyte-specific protein tyrosine kinase/JAK3-
dependent activation of the PI3K/AKT pathway with little or no involvement of STAT5, NF-kB, or the calcineurin/NFAT pathways.
Such signaling induces marked proliferation associated with rapid and selective expression of eomesodermin but not T-bet and
differentiation into long-lived central memory cells after adoptive transfer. The Journal of Immunology, 2013, 191: 5559–5573.116171sciescopu
Naïve CD8 + T cell derived tumor-specific cytotoxic effectors as a potential remedy for overcoming TGF-β immunosuppression in the tumor microenvironment
Full text linkDespite of the potential implications for cancer immunotherapy, conventional approaches using in vitro expanded CD8 + T cells have suboptimal outcomes, mostly due to loss of functionality from cellular exhaustion. We therefore investigated the phenotypic and functional differences among in vitro activated CD8 + T cells of three different sources, namely naïve (NT eff), memory (MT eff) and tumor-infiltrating lymphocytes (TIL eff) from human and mice, to better understand mechanisms behind potent effector functions and potential for overcoming current limitations. In line with the greater proliferation activity and longer telomere lengths of NT eff populations, cells of naïve origin exhibited significantly less amounts of T cell exhaustion markers than those of MT eff and TIL eff, and moreover, acquired distinct expression patterns of memory-promoting transcription factors, T-bet and Eomes, induced in a rapid and sustainable manner. NT eff cells appeared to have lower expression of Foxp1 and were refractory to apoptosis upon TGF-β conditioning, implying better survival potential and resistance to tumor-induced immune suppression. Of CD8 + T cell pools activated to tumor-specific CTLs, naïve cell generated effectors possessed the most potent cytotoxic activity, validating implications for use in rational design of adoptive immunotherapy11091sciescopu
Transcription Factor KLF10 Constrains IL-17-Committed Vγ4+ γδ T Cells
Full text linkγδ T cells, known to be an important source of innate IL-17 in mice, provide critical contributions to host immune responses. Development and function of γδ T cells are directed by networks of diverse transcription factors (TFs). Here, we examine the role of the zinc finger TFs, Kruppel-like factor 10 (KLF10), in the regulation of IL-17-committed CD27− γδ T (γδ27−-17) cells. We found selective augmentation of Vγ4+ γδ27− cells with higher IL-17 production in KLF10-deficient mice. Surprisingly, KLF10-deficient CD127hi Vγ4+ γδ27−-17 cells expressed higher levels of CD5 than their wild-type counterparts, with hyper-responsiveness to cytokine, but not T-cell receptor, stimuli. Thymic maturation of Vγ4+ γδ27− cells was enhanced in newborn mice deficient in KLF10. Finally, a mixed bone marrow chimera study indicates that intrinsic KLF10 signaling is requisite to limit Vγ4+ γδ27−-17 cells. Collectively, these findings demonstrate that KLF10 regulates thymic development of Vγ4+ γδ27− cells and their peripheral homeostasis at steady state
Alveolar Macrophages Treated With Bacillus subtilis Spore Protect Mice Infected With Respiratory Syncytial Virus A2
Full text linkRespiratory syncytial virus (RSV) is a major pathogen that infects lower respiratory tract and causes a common respiratory disease. Despite serious pathological consequences with this virus, effective treatments for controlling RSV infection remain unsolved, along with poor innate immune responses induced at the initial stage of RSV infection. Such a poor innate defense mechanism against RSV leads us to study the role of alveolar macrophage (AM) that is one of the primary innate immune cell types in the respiratory tract and may contribute to protective responses against RSV infection. As an effective strategy for enhancing anti-viral function of AM, this study suggests the intranasal administration of Bacillus subtilis spore which induces expansion of AM in the lung with activation and enhanced production of inflammatory cytokines along with several genes associated with M1 macrophage differentiation. Such effect by spore on AM was largely dependent on TLR-MyD88 signaling and, most importantly, resulted in a profound reduction of viral titers and pathological lung injury upon RSV infection. Taken together, our results suggest a protective role of AM in RSV infection and its functional modulation by B. subtilis spore, which may be a useful and potential therapeutic approach against RSV. © 2019 Hong, Kye, Park, Cheon, Chu, Park, Park, Chang, Cho, Song, Han
and Yun
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