Control of self‐reactive cytotoxic T lymphocytes expressing γδ T cell receptors by natural killer inhibitory receptors

Halary, Franck; Peyrat, Marie-Alix; Champagne, Éric; López‐Botet, Miguel; Moretta, Alessandro; Vié, Henri; Fournié, Jean Jacques; Bonneville, Marc

doi:10.1002/eji.1830271111

Cited by 145 publications

(134 citation statements)

References 41 publications

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“…2), this Vc4/Vd5 T cell population displayed a heterogeneous MHC-NKR phenotype. This concerned both the lectin-and Ig-like MHC-NKR, even though the first was quantitatively more expressed than the second, as previously observed for polyclonal peripheral blood cd T lymphocytes [24]. This observation lends further support to the conclusions deduced from the results previously obtained on clones generated in vitro [9][10][11], because it has the advantage to be done on freshly isolated PBMC.…”

Section: Discussionsupporting

confidence: 88%

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Expression of MHC class I receptors confers functional intraclonal heterogeneity to a reactive expansion of γδ T cells

et al. 2005

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NK cell receptors for MHC class I molecules (MHC-NKR) can be expressed by T cell subsets. The restricted repertoire and phenotypic characteristics of MHC-NKR + T cells indicate that expression of MHC-NKR is acquired upon antigenic challenge and might promote expansion of T cells. Previous studies performed on in vitro generated ab T cell clones concluded that MHC-NKR expression was not a clonal attribute. Here, we examined a massive monoclonal expansion of a non-leukemic cd T cell population found in the peripheral blood of a lung-transplanted patient who suffered from a cytomegalovirus infection. Despite their monoclonality, these T cells displayed a heterogeneous and stable in vivo Ig-and lectin-like MHC-NKR phenotype. Twenty percent of the cells displayed a CD94 + NKG2A + phenotype, and 10% were labeled with an anti-CD158b1/b2/j monoclonal antibody. A CD158b/j + cd T cell clone derived in vitro from patient's peripheral blood lymphocytes was shown to express the activating form CD158j (KIR2DS2), which once cross-linked stimulated the clone cytolytic function and costimulated the TCR-induced production of cytokines, independently of the killer-activating receptor-associated protein (KARAP). In conclusion, heterogeneity of MHC-NKR expression confers a functional intraclonal diversity that may participate to induction of specific cd T cell effector functions or proliferation upon pathogen challenge.

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Section: Discussionsupporting

confidence: 88%

“…The cytolytic activity of Vc4/Vd5 T cell clones was tested in a redirected killing assay using FcRc + P815 target cells and a standard 4-h 51 Cr-release assay as previously described [24].…”

Section: Redirected Killing Assaymentioning

confidence: 99%

Expression of MHC class I receptors confers functional intraclonal heterogeneity to a reactive expansion of γδ T cells

et al. 2005

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“…The above effects could not be observed with JAR-G1m but with JAR-E, suggesting that anti-CD94 treatment affects the CD94-HLA-E interaction. Increased cytotoxic activity despite the reduced conjugation capacity can possibly be explained by an altered cytokine production resulting from inhibition of the KIR HLA-E interaction (42). The anti-CD94 mAb inhibits the V␥9V␦2 T cell proliferation in response to mycobacterial phosphoantigens and also the HIV-induced V␥9V␦2 T cell expansion (22).…”

Section: Discussionmentioning

confidence: 99%

Recognition of Nonclassical HLA Class I Antigens by γδ T Cells During Pregnancy

Barakonyi

Kovács

Mikó

et al. 2002

The Journal of Immunology

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The healthy trophoblast does not express classical HLA-A and HLA-B products; therefore, an MHC-restricted recognition of trophoblast-presented Ags is unlikely. In the decidua and also in peripheral blood of healthy pregnant women, γδ T cells significantly increase in number. We investigated the possible role of γδ T cells in recognition of trophoblast-presented Ags. PBL and isolated γδ T cells from healthy pregnant women as well as from those at risk for premature pregnancy termination were conjugated to choriocarcinoma cells (JAR) transfected with nonclassical HLA Ags (HLA-E, HLA-G). To investigate the involvement of killer-inhibitory/killer-activatory receptors in trophoblast recognition, we tested the effect of CD94 block on cytotoxic activity of Vδ2+ enriched γδ T cells to HLA-E- and/or HLA-G-transfected targets. Lymphocytes from healthy pregnant women preferentially recognized HLA− choriocarcinoma cells, whereas those from pathologically pregnant patients did not discriminate between HLA+ and HLA− cells. Normal pregnancy Vδ2+ T cells conjugated at a significantly increased rate to HLA-E transfectants, whereas Vδ2+ lymphocytes from pathologically pregnant women did not show a difference between those and HLA− cells. Blocking of the CD94 molecule of Vδ2+ lymphocytes from healthy pregnant women resulted in an increased cytotoxic activity to HLA-E-transfected target cells. These data indicate that Vδ2+ lymphocytes of healthy pregnant women recognize HLA-E on the trophoblast, whereas Vδ1 cells react with other than HLA Ags. In contrast to Vδ2+ lymphocytes from healthy pregnant women, those from women with pathological pregnancies do not recognize HLA-E via their killer-inhibitory receptors and this might account for their high cytotoxic activity.

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“…[8][9][10] Like NK cells, human cd T cells express activating receptors, such as NKG2D that recognizes stress-inducible MHC class I-related MICA/MICB molecules and the UL16-binding proteins that are upregulated on malignant or stressed cells and induce cytolysis, 11,12 and they are inhibited by the expression of killer Ig-like receptors, which bind certain MHC class I alleles expressed by nonmalignant cells and trophoblasts. [13][14][15] However, the versatility of cd T cells is further extended by their demonstrated ability to assume the role and appearance of professional antigen presenting cells. 16,17 This unusual functional plasticity has given the impression that these multitalented T cells are 'Jacks of all-trades, but masters of none', and they are sometimes erroneously delegated to a niche occupied by vestigial features of modern anatomy by some who are left confounded as to their real purpose.…”

Section: Prologuementioning

confidence: 99%

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

2012

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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...

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Control of self‐reactive cytotoxic T lymphocytes expressing γδ T cell receptors by natural killer inhibitory receptors

Cited by 145 publications

References 41 publications

Expression of MHC class I receptors confers functional intraclonal heterogeneity to a reactive expansion of γδ T cells

Expression of MHC class I receptors confers functional intraclonal heterogeneity to a reactive expansion of γδ T cells

Recognition of Nonclassical HLA Class I Antigens by γδ T Cells During Pregnancy

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

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