Differentiation of human γδ T cells towards distinct memory phenotypes

Eberl, Matthias; Engel, Rosel; Beck, Ewald; Jomaa, Hassan

doi:10.1016/s0008-8749(02)00519-1

Cited by 70 publications

(80 citation statements)

References 20 publications

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“…Depending on the culture conditions, Vc9/Vd2 T cells clearly assume different functions including distinct cytokine profiles [49,74,72,[124][125][126], and hence more research is needed to delineate whether Vc9/Vd2 T-APCs may induce different 'flavors' of CD4 + T cell responses (Th1, Th2, Th17, Th22, Treg), and what the signals involved in such a polarization are. In this respect, our preliminary findings suggest that under appropriate conditions Vc9/Vd2 T-APCs are able to induce considerable IL-22 expression in naive CD4 + T cells [C.J.T., M.E.…”

Section: Priming Of Cd4 + and Cd8 + T Cells By Vc9/vd2 T Cells: A Newmentioning

confidence: 99%

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Tyler

Doherty

Moser

et al. 2015

Cellular Immunology

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a b s t r a c tUnconventional T cells are gaining center stage as important effector and regulatory cells that orchestrate innate and adaptive immune responses. Human Vc9/Vd2 T cells are amongst the best understood unconventional T cells, as they are easily accessible in peripheral blood, can readily be expanded and manipulated in vitro, respond to microbial infections in vivo and can be exploited for novel tumor immunotherapies. We here review findings that suggest that Vc9/Vd2 T cells, and possibly other unconventional human T cells, play an important role in bridging innate and adaptive immunity by promoting the activation and differentiation of various types of antigen-presenting cells (APCs) and even turning into APCs themselves, and thereby pave the way for antigen-specific effector responses and long-term immunological memory. Although the direct physiological relevance for most of these mechanisms still needs to be demonstrated in vivo, these findings may have implications for novel therapies, diagnostic tests and vaccines.Ó 2015 Published by Elsevier Inc. Introduction cd T cells represent a third lineage of lymphocytes expressingre-arranged antigen receptors that co-evolved with 'classical' B cells and ab T cells over 400 million years, arguing for a crucial and non-redundant contribution of each lymphocyte to effective immune responses, and hence the evolutionary survival of all jawed vertebrate species [1]. 30 years have passed since the accidental and unexpected cloning of the cd T cell receptor (TCR) and the subsequent realization that ab T cells and cd T cells are fundamentally different with respect to the types of antigens they recognize and the distinct effector functions triggered upon such recognition. However, the manifold contributions of cd T cells to homeostasis, inflammation, infection and tumor surveillance have historically been neglected and are only beginning to be integrated into comprehensive models of the immune system [1][2][3][4][5][6][7].1. Innate-like pattern recognition by human Vc9/Vd2 T cells Like other 'unconventional' T cells carrying an ab TCR such as mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells, cd T cells are characterized by a markedly restrictedTCR usage that allows them to recognize self and non-self molecules in the absence of classical antigen presentation via MHC I or MHC II. Vc9/Vd2 + cd T cells represent the major cd T cell subset in human peripheral blood where they typically comprise 1-5% in healthy adults [8]. In many microbial infections, Vc9/Vd2 T cells increase locally and/or systemically [9,10] and can reach in excess of 50% of all peripheral T cells within a matter of days [11], revealing a fundamental role of this unconventional T cell population in acute disease and suggesting their exploitation for diagnostic and therapeutic purposes [12][13][14]. Vc9/Vd2 T cells uniformly respond to a class of low molecular weight molecules often referred to as 'phosphoantigens' that represent metabolites of the isoprenoid biosynthesis...

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Section: Priming Of Cd4 + and Cd8 + T Cells By Vc9/vd2 T Cells: A Newmentioning

confidence: 99%

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Tyler

Doherty

Moser

et al. 2015

Cellular Immunology

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“…Cells were harvested at appropriate time-points, and analysed on a four-colour Epics XL flow cytometer supported with EXPO32 ADC software (Beckman Coulter, Krefeld, Germany) 26 Optimal compensation and gain settings were determined for each experiment using unstained, single-stained and multistained samples. Gates were set on live CD3 + lymphocytes based upon their appearance in forward/ side-scatter and the corresponding fluorescence patterns; apoptotic and necrotic cells were largely excluded by these settings, as confirmed by counterstainings with propidium iodide and annexin V (Beckman Coulter).…”

Section: Flow Cytometry Analysismentioning

confidence: 99%

Interferon‐β therapy reduces CD4⁺ and CD8⁺ T‐cell reactivity in multiple sclerosis

et al. 2006

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Summary Therapy with interferon‐β (IFN‐β) has well‐established clinical effects in multiple sclerosis (MS), albeit the immunomodulatory mechanisms are not fully understood. We assessed the prevalence and functional capacity of CD4+ and CD8+ T cells in healthy donors, and in untreated and IFN‐β‐treated MS patients, in response to myelin oligodendrocyte glycoprotein (MOG). The proportion of CD45RO+ memory T cells was higher in MS patients than in healthy donors, but returned to normal values upon therapy with IFN‐β. While CD45RO+ CD4+ T cells from all three groups responded to MOG in vitro, untreated patients showed augmented proliferative responses compared to healthy individuals and IFN‐β treatment reduced this elevated reactivity back to the values observed in healthy donors. Similarly, the response of CD45RO+ CD8+ T cells to MOG was strongest in untreated patients and decreased to normal values upon immunotherapy. Overall, the frequency of peripheral CD45RO+ memory T cells ex vivo correlated with the strength of the cellular in vitro response to MOG in untreated patients but not in healthy donors or IFN‐β‐treated patients. Compared with healthy individuals, responding CD4+ and CD8+ cells were skewed towards a type 1 cytokine phenotype in untreated patients, but towards a type 2 phenotype under IFN‐β therapy. Our data suggest that the beneficial effect of IFN‐β in MS might be the result of the suppression or depletion of autoreactive, pro‐inflammatory memory T cells in the periphery. Assessment of T‐cell subsets and their reactivity to MOG may represent an important diagnostic tool for monitoring successful immunotherapy in MS.

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“…However, based primarily on in vitro studies, IL-21 exhibits a broad capacity to regulate lymphoid cell functions. For T lymphocytes, IL-21 somewhat costimulates proliferation by anti-CD3-activated T cells, augments allospecific CTL activity by CD8 ϩ T cells, and promotes the differentiation of V␥9/V␦2 T cells into central memory CD45RO ϩ T cells (8,9,11). IL-21 is preferentially produced by Th2 cells and in turn inhibits the development of IFN-␥-producing Th1 cells, in part by decreasing the responsiveness of developing Th cells to IL-12 (12).…”

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confidence: 99%

Distinct Activation Signals Determine whether IL-21 Induces B Cell Costimulation, Growth Arrest, or Bim-Dependent Apoptosis

Jin

Carrió

et al. 2004

The Journal of Immunology

239

282

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IL-21 costimulates B cell proliferation and cooperatively with IL-4 promotes T cell-dependent Ab responses. Somewhat paradoxically, IL-21 also induces apoptosis of B cells. The present study was undertaken to more precisely define the expression of the IL-21R, using a novel mAb, and the circumstances by which IL-21 promotes B cell growth vs death. The IL-21R was first detected during T and B cell development, such that this receptor is expressed by all mature lymphocytes. The IL-21R was further up-regulated after B and T activation, with the highest expression by activated B cells. Functional studies demonstrated that IL-21 substantially inhibited proliferation and induced Bim-dependent apoptosis for LPS or CpG DNA-activated B cells. In contrast, IL-21 induced both costimulation and apoptosis for anti-CD40-stimulated B cells, whereas IL-21 primarily costimulated B cells activated by anti-IgM or anti-IgM plus anti-CD40. Upon blocking apoptosis using C57BL/6 Bim-deficient or Bcl-2 transgenic B cells, IL-21 readily costimulated responses to anti-CD40 while proliferation to LPS was still inhibited. Engagement of CD40 or the BCR plus CD40 prevented the inhibitory effect by IL-21 for LPS-activated B cells. Collectively, these data indicate that there are three separable outcomes for IL-21-stimulated B cells: apoptosis, growth arrest, or costimulation. We favor a model in which IL-21 promotes B cell maturation during a productive T cell-dependent B cell response, while favoring growth arrest and apoptosis for nonspecifically or inappropriately activated B cells.

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Differentiation of human γδ T cells towards distinct memory phenotypes

Cited by 70 publications

References 20 publications

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Interferon‐β therapy reduces CD4⁺ and CD8⁺ T‐cell reactivity in multiple sclerosis

Distinct Activation Signals Determine whether IL-21 Induces B Cell Costimulation, Growth Arrest, or Bim-Dependent Apoptosis

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Differentiation of human γδ T cells towards distinct memory phenotypes

Cited by 70 publications

References 20 publications

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Interferon‐β therapy reduces CD4+ and CD8+ T‐cell reactivity in multiple sclerosis

Distinct Activation Signals Determine whether IL-21 Induces B Cell Costimulation, Growth Arrest, or Bim-Dependent Apoptosis

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Interferon‐β therapy reduces CD4⁺ and CD8⁺ T‐cell reactivity in multiple sclerosis