Shared reactivity of Vδ2neg γδ T cells against cytomegalovirus-infected cells and tumor intestinal epithelial cells

Halary, Franck; Pitard, Vincent; Dłubek, Dorota; Krzysiek, Roman; Merville, Pierre; Dromer, C.; Émilie, Dominique; Moreau, Jean-François; Déchanet‐Merville, Julie

doi:10.1084/jem.20041851

Cited by 206 publications

(247 citation statements)

References 40 publications

Supporting

Mentioning

226

Contrasting

Order By: Relevance

“…In CMV-infected patients after kidney transplantation, V␦2-negative ␥␦ T cells show a long-lasting expansion and display a strong reactivity against CMV-infected cells (8,41). This reactivity requires TCR engagement.…”

Section: Discussionmentioning

confidence: 99%

Direct Costimulatory Effect of TLR3 Ligand Poly(I:C) on Human γδ T Lymphocytes

Wesch

Beetz

Oberg

et al. 2006

The Journal of Immunology

153

141

View full text Add to dashboard Cite

TLR3 recognizes viral dsRNA and its synthetic mimetic polyinosinic-polycytidylic acid (poly(I:C)). TLR3 expression is commonly considered to be restricted to dendritic cells, NK cells, and fibroblasts. In this study we report that human γδ and αβ T lymphocytes also express TLR3, as shown by quantitative real-time PCR, flow cytometry, and confocal microscopy. Although T cells did not respond directly to poly(I:C), we observed a dramatic increase in IFN-γ secretion and an up-regulation of CD69 when freshly isolated γδ T cells were stimulated via TCR in the presence of poly(I:C) without APC. IFN-γ secretion was partially inhibited by anti-TLR3 Abs. In contrast, poly(I:C) did not costimulate IFN-γ secretion by αβ T cells. These results indicate that TLR3 signaling is differentially regulated in TCR-stimulated γδ and αβ T cells, suggesting an early activation of γδ T cells in antiviral immunity.

show abstract

Section: Discussionmentioning

confidence: 99%

Direct Costimulatory Effect of TLR3 Ligand Poly(I:C) on Human γδ T Lymphocytes

Wesch

Beetz

Oberg

et al. 2006

The Journal of Immunology

153

141

View full text Add to dashboard Cite

show abstract

“…Non-CD1-restricted Vd1 + T cells recognize and kill a variety of tumor cells [206][207][208] and cells infected with CMV [209,210] and HIV [211,212], and release cytokines in response to bacteria and fungi [213,214]. Once activated, Vd1 + T cells can drive DC maturation [215] but also kill DCs [216].…”

Section: Innate Regulation Of Adaptive Immune Responses: Vd2 + Versusmentioning

confidence: 99%

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

Tyler

Doherty

Moser

et al. 2015

Cellular Immunology

View full text Add to dashboard Cite

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...

show abstract

“…The majority of the tissueassociated cd T cells bear the Vd1 TCR with Vd3 and Vd5 making up minor populations. 32,33 In the literature, these are often collectively called the 'non-Vd2' cd T cells. In addition to their role in maintaining immune homeostasis in the local microenvironment, 25 tissueassociated cd T cells, in both mice and men, play an important function in wound healing, removing distressed or transformed epithelial cells and subduing excessive inflammation.…”

Section: Missingmentioning

confidence: 99%

“…90,91 It is therefore feasible that this change in cd T cell distribution observed in never-infected individuals from this West African population stems from evolutionary selection based on an immune advantage by those having a high proportion of Vd1 T cells-which would again align with the association of there being some adaptive influence of microbial exposure on the make-up of cd T cells in an organism. Other infectious diseases that are associated with the recruitment and expansion of specifically the Vd1 T cell subset in the periphery are cytomegalovirus, 33,92 Epstein-Barr virus 93,94 and HIV. 95,96 In most of these cases, the specific activation and expansion appears to be driven by the presentation of endogenous molecules rather than virally derived antigens-keeping with the notion that these T cells are particularly well adapted to sensing the turmoil within rather than relying exclusively on external validation.…”

Section: Defined By Experiences Tainted By Innate Tendenciesmentioning

confidence: 99%

Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic

2012

View full text Add to dashboard Cite

The elusive task of defining the character of cd T cells has been an evolving process for immunologists since stumbling upon their existence during the molecular characterization of the a and b T cell receptor genes of their better understood brethren. Defying the categorical rules used to distinctly characterize lymphocytes as either innate or adaptive in nature, cd T cells inhabit a hybrid world of their own. At opposing ends of the simplified spectrum of modes of antigen recognition used by lymphocytes, natural killer and ab T cells are particularly well equipped to respond to the 'missing self' and the 'dangerous non-self', respectively. However, between these two reductive extremes, we are chronically faced with the challenge of making peace with the 'safe non-self' and dealing with the inevitable 'distressed self', and it is within this more complex realm cd T cells excel thanks to their highly empathetic nature. This review gives an overview of the latest insights revealing the unfolding story of human cd T cells, providing a biographical sketch of these unique lymphocytes in an attempt to capture the essence of their fundamental nature and events that influence their life trajectory. What hangs in their balance is their nuanced ability to differentiate the friends from the foe and the pathological from the benign to help us adapt swiftly and efficiently to life's many stresses. Keywords: antigen recognition; danger-associated molecular patterns; gamma delta T cell subsets; immune homeostasis; innate immunity; stress response PROLOGUE Since the time of their accidental discovery during the molecular characterization of the a and b T cell receptor (TCR) genes belonging to their relatively unambiguous brethren, 1 'enigmatic' is still one of the most commonly used adjectives to describe cd T cells. This can be attributed to the fact that these unconventional lymphocytes have thus far been remarkably successful in thwarting most attempts at definition. Much of what we know about T cell biology and function comes from what has been discerned through studies done on ab T cells; however, one thing that is certain is that the majority of the rules governing the lives of ab T cells are surprisingly irrelevant when it comes to understanding the elusive character of cd T cells. Table 1 highlights some of the major differences between these two T cell subsets in humans.Recognition by cd T cells is not typically in the context of classical major histocompatibility complex (MHC) class I or II molecules and neither is antigen processing required. 2,3 These observations are corroborated by the fact that the majority of cd T cells are CD8 and CD4 negative. Crystal structure analysis of the cd TCR determined that the length and conformation of cd TCR resemble immunoglobulins (Ig) more than the ab TCR, which was taken to suggest that antigen recognition by cd T cells may be more similar to the binding of antibody to antigen rather than the MHC/peptide complex recognized by ab T cells. 4 The very basis of foreign antigen rec...

show abstract

Shared reactivity of Vδ2neg γδ T cells against cytomegalovirus-infected cells and tumor intestinal epithelial cells

Cited by 206 publications

References 40 publications

Direct Costimulatory Effect of TLR3 Ligand Poly(I:C) on Human γδ T Lymphocytes

Direct Costimulatory Effect of TLR3 Ligand Poly(I:C) on Human γδ T Lymphocytes

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

Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic

Contact Info

Product

Resources

About