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Origin of CD8^+ effector and Memory t cell Subsets

cellular & Molecular Immunology 2007年第6期4卷 399-405页

作者： Christian Stemberger Michael Neuenhahn Veit R.Buchholz Dirk H.Busch Institute for Medical Microbiology Immunology and HygieneTechnical University Munich Clinical Cooperation Group"Antigen-Specific Immunotherapy"and"Immune-Monitoring" Helmholtz Center Munich–Germany ResearchCenter for Environment Health and Technical University MunichGermany

It is well accepted that CD8＋ t cells play a pivotal role in providing protection against infection with intracellular pathogens and some tumors. In many cases protective immunity is maintained for long periods of time （immunological memory）. Over the past years, it has become evident that in order to fulfill these multiple tasks, distinct subsets of effector and memory t cells have to be generated. Until today, however, little is known about the underlying mechanisms of subset differentiation and the timing of lineage fate decisions. In this context, it is of special importance to determine at which level of clonal expansion functional and phenotypical heterogeneity is achieved. Different models for t cell subset diversification have been proposed; these differ mainly in the time point during priming and clonal expansion （prior, during, or beyond the first cell division） when differentiation programs are induced. Recently developed single-cell adoptive transfer technology has allowed us to demonstrate that individual precursor cell still bears the full plasticity to develop into a plethora different t cell subsets. this observation targets the shaping of t cell subset differentiation towards factors that are still operative beyond the first cell division. these findings have important implications for vaccine development, as the modulation of differentiation patterns towards distinct subsets could become a powerful strategy to enhance the efficacy and quality of vaccines. cellular ＆ Molecular Immunology.

关键词： effector t cell memory t cell differentiation

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themis suppresses the effector function of CD8^(+)t cells in acute viral infection

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cellular & Molecular Immunology 2023年第5期20卷 512-524页

作者： Jian tang Xian Jia Jian Li Junchen Dong Jiayu Wang Wanyun Li Yuzhen Zhu Yanyan Hu Bowen Hou Chunjie Lin Yu Cong tong Ren Changsheng Yan Hongying Yang Qian Lai Haiping Zheng Yuzhou Bao Namrata Gautam Hong-Rui Wang Bing Xu Xiao Lei Chen Qing Li Nicholas R.J.Gascoigne Guo Fu State Key Laboratory of cellular Stress Biology School of MedicineFaculty of Medicine and Life SciencesXiamen UniversityXiamenChina School of Life Sciences Xiamen UniversityXiamenChina Immunology translational Research Programme Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Department of Microbiology and Immunology Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Department of Hematology The First Affiliated Hospital and Institute of HematologySchool of MedicineXiamen UniversityXiamenChina Cancer Research Center of Xiamen University XiamenChina

CD8^(+)t cells play a central role in antiviral immune *** infection,naive CD8^(+)t cells differentiate into effector cells to eliminate virus-infected cells,and some of these effector cells further differentiate into memory cells to provide long-term protection after infection is *** extensively investigated,the underlying mechanisms of CD+t-cell differentiation remain incompletely *** is a t-cell-specific protein that plays critical roles in t-cell *** studies using themis t-cell conditional knockout mice also demonstrated that themis is required to promote mature CD8^(+)t-cell homeostasis,cytokine responsiveness,and antibacterial *** this study,we used LCMV Armstrong infection as a probe to explore the role of themis in viral *** found that preexisting CD8^(+)t-cell homeostasis defects and cytokine hyporesponsiveness do not impair viral clearance in themis t-cell conditional knockout *** analyses showed that in the primary immune response,themis deficiency promoted the differentiation of CD8^(+)effector cells and increased their tNF and IFNy ***,themis deficiency impaired memory precursor cell(MPEC)differentiation but promoted short-lived effector cell(SLEC)*** deficiency also enhanced effector cytokine production in memory CD8^(+)t cells while impairing central memory CD8^(+)t-cell ***,we found that themis mediates PD-1 expression and its signaling in effector CD8^(+)t cells,which explains the elevated cytokine production in these cells when themis is disrupted.

关键词： themis effector t cell CD8 t-cell differentiation Cytokine LCMV

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Curcumin reverses t cell-mediated adaptive immune dysfunctions in tumor-bearing hosts

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cellular & Molecular Immunology 2010年第4期7卷 306-315页

作者： Sankar Bhattacharyya Dewan Md Sakib Hossain Suchismita Mohanty Gouri Sankar Sen Sreya Chattopadhyay Shuvomoy Banerjee Juni Chakraborty Kaushik Das Diptendra Sarkar tanya Das Gaurisankar Sa Division of Molecular Medicine Bose InstituteKolkataIndia

Immune dysfunction is well documented during tumor progression and likely contributes to tumor immune ***81 cytotoxic t lymphocytes(CtLs)are involved in antigen-specific tumor destruction and CD41 t cells are essential for helping this CD81 t cell-dependent tumor *** often target and inhibit t-cell function to escape from immune *** dysfunction includes loss of effector and memory t cells,bias towards type 2 cytokines and expansion of t regulatory(treg)*** has previously been shown to have antitumor activity and some research has addressed the immunoprotective potential of this plant-derived polyphenol in tumor-bearing *** we examined the role of curcumin in the prevention of tumor-induced dysfunction of t cell-based immune *** observed severe loss of both effector and memory t-cell populations,downregulation of type 1 and upregulation of type 2 immune responses and decreased proliferation of effector t cells in the presence of ***,in turn,prevented this loss of t cells,expanded central memory t cell(tCM)/effector memory t cell(tEM)populations,reversed the type 2 immune bias and attenuated the tumor-induced inhibition of t-cell proliferation in tumor-bearing *** investigation revealed that tumor burden upregulated treg cell populations and stimulated the production of the immunosuppressive cytokines transforming growth factor(tGF)-b and IL-10 in these ***,however,inhibited the suppressive activity of treg cells by downregulating the production of tGF-b and IL-10 in these *** importantly,curcumin treatment enhanced the ability of effector t cells to kill cancer ***,our observations suggest that the unique properties of curcumin may be exploited for successful attenuation of tumor-induced suppression of cell-mediated immune responses.

关键词： CD41/CD81 t cell effector t cell t-regulatory cell FoxP3 th1/th2

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