Expansion and Function of CD8+ T Cells Expressing Ly49 Inhibitory Receptors Specific for MHC Class I Molecules

Anfossi, Nicolas; Robbins, Scott H.; Ugolini, Sophie; Georgel, Philippe; Hoebe, Kasper; Bouneaud, Cécile; Ronet, Catherine; Kaser, Arthur; DiCioccio, Catherine B.; Tomasello, Elena; Blumberg, Richard S.; Beutler, Bruce; Reiner, Steven L.; Alexopoulou, Lena; Lantz, Olivier; Raulet, David H.; Brossay, Laurent; Vivier, Éric

doi:10.4049/jimmunol.173.6.3773

Cited by 31 publications

(30 citation statements)

References 60 publications

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“…In this respect, chronic antigenic exposure has been shown to induce MHC-NKR expression on mouse CD8 T cells [6]. It is thus tempting to speculate that the chronic CMV infection, which persisted for 20 months in this patient, led to MHC-NKR expression on the cd T cells involved in the antiviral immune response.…”

Section: Discussionmentioning

confidence: 82%

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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: Discussionmentioning

confidence: 82%

“…In mice, expansion of self-reactive CD8 + T cells expressing an inhibitory MHC-NKR Ly49 was obtained upon persistent challenge with a self antigen [6]. Altogether, these observations suggest that MHC-NKR expression is acquired after antigenic stimulation and is associated with expansion and survival of T cells.…”

Section: Introductionmentioning

confidence: 82%

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 only reported mechanism of inducing Ly49 receptor expression on T cells, which had defined ligand specificity, used a model of chronic T cell stimulation. In this model, female CD8 + T cells, which express transgenic TCR recognizing the male HY antigen, up-regulate Ly49 expression when transferred to male Rag-deficient recipients, but this only occurs if HY-specific CD4 T cells are co-transferred [27]. One further piece of evidence for an activation-induced NK programming by mouse cd T cells is seen in the skewing of the TCR repertoire.…”

Section: Discussionmentioning

confidence: 99%

“…At the immature DX5 -stage, NK cells express multiple NK receptors including CD94/NKG2, NKG2D and NKp46, but are unable to perform granule-mediated cytotoxicity [21][22][23]. During maturation to DX5 + mature cells, NK cells start to express Ly49 MHC class I receptors [22][23][24], and undergo an education process during which NK cells expressing inhibitory receptors that recognize self MHC class I are "licensed" to perform more potent effector functions [25][26][27][28].cd T cells, like ab T cells, develop in the thymus, where V(D)J recombination of TCR genes occurs. Using T cell receptor d locus-histone 2B-enhanced GFP (Tcrd-H2BEGFP) knock-in mice in which an IRES-controlled H2B-EGFP fusion protein is present in the 3 0 untranslated region of the Tcrd constant gene [29], we have recently shown that developing cd T cells undergo a "TCR quality control checkpoint" upon successful expression of TCRcd.…”

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confidence: 99%

Germ‐line and rearranged Tcrd transcription distinguish bona fide NK cells and NK‐like γδ T cells

et al. 2007

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NK cells and cd T cells are distinct subsets of lymphocytes that contextually share multiple phenotypic and functional characteristics. However, the acquisition and the extent of these similarities remain poorly understood. Here, using T cell receptor d locus-histone 2B-enhanced GFP (Tcrd-H2BEGFP) reporter mice, we show that germline transcription of Tcrd occurs in all maturing NK cells. We also describe a population of mouse NK-like cells that are indistinguishable from "bona fide" NK cells using standard protocols. Requirements for V(D)J recombination and a functional thymus, along with very low-level expression of surface TCRcd but high intracellular CD3, define these cells as cd T cells. "NK-like cd T cells" are CD127 + , have a memory-activated phenotype, express multiple NK cell receptors and readily produce interferon-c in response to IL-12/IL-18 stimulation. The close phenotypic resemblance between NK cells and NK-like cd T cells is a source of experimental ambiguity in studies bridging NK and T cell biology, such as those on thymic NK cell development. Instead, it ascribes chronic TCRcd engagement as a means of acquiring NK-like function. IntroductionClassification of NK cells and some cd T cell subsets as innate immune cells is argued by their recognition and response to self ligands and microbial molecules without any requirement for prior specific immunization [1][2][3][4][5]. NK cells are mediators of immunity against various infectious diseases and tumor cells, performing direct cell-mediated cytotoxicity and producing cytokines in response to cell-associated and soluble stimuli [6,7]. They additionally shape adaptive immune responses, mainly through the production of cytokines [8]. Their activation is regulated through germ-line-encoded receptors including NKG2D, the natural cytotoxicity receptors and inhibitory receptors for MHC class I, many of which recognize self-encoded ligands [9][10][11]. Most cd T cell subsets are unconventional T cells that -similar to CD1d-restricted Va14i NKT cells, MR1-restricted MAIT cells and certain populations of CD8 + T cells -are not restricted to classical MHC class I-or MHC class II-bearing specific peptides [2,3]. They have heterogeneous effector functions associated with differential TCRcd usage. Roles have been described in immunity against infectious pathogens and tumors [12] and cd T cells have been strongly implicated in immunosuppressive regulation of the immune system and in the process of wound healing [13,14]. Using TCR transfer experiments, or direct ligand binding, TCRcd ligands have been described for a small number of subsets [5]. In the mouse, cd T cell subsets recognize the non-classical MHC class I molecules T10/T22 [15], and an unknown ligand expressed by keratinocytes [16]. In humans, some Vd1 cd T cells recognize non-classical MHC class I molecules MICA and MICB, and Vc9Vd2 cd T cells have been reported to recognize self and bacterial phosphoantigens, and a complex formed between F1-ATP synthase and apolipoprotein A-1 [5,[17][18][19][20].Du...

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“…ϩ T cells that express other NKRs (Ly49 or killer immunoglobulinlike receptors), display reduced frequencies of IFN-␥ and TNF-␣ expression compared with NKR Ϫ CD8 ϩ T cells [43,44], whereas Kambayashi et al reported that murine influenza-specific NKR ϩ T cells produce IFN-␥ in response to influenza antigens [45].…”

Section: Cd56mentioning

confidence: 99%

Activation-Induced Expression of CD56 by T Cells Is Associated With a Reprogramming of Cytolytic Activity and Cytokine Secretion Profile In Vitro

et al. 2006

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A subset of human T lymphocytes expresses the natural killer (NK) cell-associated receptor CD56 and is capable of major histocompatibility complex (MHC)-unrestricted cytotoxicity against a variety of autologous and allogeneic tumor cells. ϩ T cells expressed IFN-␥, IL-4, and IL-13 within hours of activation. These acquired cytolytic and cytokine secretion activities of CD56 ϩ T cells make them potential targets for immunotherapy for infectious and immune-mediated disease.

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Expansion and Function of CD8+ T Cells Expressing Ly49 Inhibitory Receptors Specific for MHC Class I Molecules

Cited by 31 publications

References 60 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

Germ‐line and rearranged Tcrd transcription distinguish bona fide NK cells and NK‐like γδ T cells

Activation-Induced Expression of CD56 by T Cells Is Associated With a Reprogramming of Cytolytic Activity and Cytokine Secretion Profile In Vitro

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