γδ T‐cell receptors: functional correlations

O’Brien, Rebecca L.; Roark, Christina L.; Jin, Niyun; Aydintug, M. Kemal; French, Jena D.; Chain, Jennifer L.; Wands, J. M.; Johnston, Molly; Born, Willi K.

doi:10.1111/j.1600-065x.2006.00477.x

Cited by 92 publications

(111 citation statements)

References 94 publications

(103 reference statements)

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“…Expansion of the  T-cell subset has been also documented in the context of various infections including Mycobacterium and cytomegalovirus [20]. However [21]. At birth, the repertoire of  T cells in cord blood is broad with no apparent restriction [22].…”

Section: Discussionmentioning

confidence: 99%

Clonal expansion of Epstein–Barr virus (EBV)-infected γδ T cells in patients with chronic active EBV disease and hydroa vacciniforme-like eruptions

et al. 2012

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Section: Discussionmentioning

confidence: 99%

Clonal expansion of Epstein–Barr virus (EBV)-infected γδ T cells in patients with chronic active EBV disease and hydroa vacciniforme-like eruptions

et al. 2012

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“…2F). Interestingly, V␥1.1 ϩ V␦6.3 ϩ ␥␦ T cells are the predominant subset of ␥␦ NKT cells, and readily produce effector cytokines (17,21,22).…”

Section: Itk ؊/؊ Mice Contain Increased Proportions Of ␥␦ T Cells Submentioning

confidence: 99%

“…Basal levels of IFN␥ mRNA were similar between the WT and Itk Ϫ/Ϫ ␥␦ T cells; after stimulation, both cell types produced IFN␥, although WT ␥␦ T cells showed higher levels of IFN␥ mRNA compared with ␥␦ T cells lacking Itk. Based on the high proportion of V␥1.1 ϩ V␦6.3 ϩ ␥␦ T cells present in Itk Ϫ/Ϫ mice and the previous association of this ␥␦ T cell subset with dual production of IL-4 and IFN␥ (21,22), we also examined WT and Itk Ϫ/Ϫ ␥␦ T cells for expression of the transcription factor PLZF. PLZF has recently been found to be critical for the development and effector function of TCR␣␤ ϩ NKT cells, where it promotes the simultaneous production of IL-4 and IFN␥ (18,19).…”

Section: Itk ؊/؊ Mice Contain Increased Proportions Of ␥␦ T Cells Submentioning

confidence: 99%

Tec kinase Itk in γδT cells is pivotal for controlling IgE production in vivo

Felices

Yin

Kosaka

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

114

145

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T cell development ͉ T cell differentiation ͉ T cell signaling T he Tec family tyrosine kinase Itk is important for signaling downstream of the T cell receptor (1). In particular, Itkdeficient T cells have defects in phospholipase C-␥ (PLC-␥) phosphorylation, calcium mobilization, mitogen-activated protein kinase (MAP kinase) activation, and AP-1 and nuclear factor of activated T cells (NFAT) activation after T cell receptor (TCR) stimulation. Itk is also critical for conventional ␣␤ T cell development, selection, and function. Of particular importance, Itk signaling regulates CD4 ϩ T helper cell differentiation, playing a key role in the development of Th2 responses (2). Based on this welldocumented defect of Itk Ϫ/Ϫ mice in generating Th2 effector responses and cytokine production, it was surprising to discover that these mice had spontaneously elevated levels of serum IgE (3, 4), as B cell isotype switching to IgE is highly dependent on Th2 cytokines IL-4 and IL-13 (5). As our previous studies had indicated that Itk Ϫ/Ϫ ␣␤ TCR ϩ NKT cells (referred to as ␣␤ NKT cells) were also highly defective in producing effector cytokines such as IL-4 (6), we considered the possibility that ␥␦ TCR ϩ NKT cells were the major source of Th2 cytokines in Itk Ϫ/Ϫ mice.The ␥␦ T cells are a highly conserved subset of T cells that constitutes 1-5% of the lymphocytes in the blood and peripheral organs of mice but can account for up to 50% of the lymphocytes in the mucosal epithelia. As with other subsets of ''innate'' T cells, ␥␦ T cells express memory cell surface markers (7), and are capable of rapidly secreting effector cytokines (8). Among the many functions attributed to ␥␦ T cells, a great deal of recent interest has focused on their ability to modulate adaptive immune responses, specifically the humoral response (9).A variety of studies have indicated that ␥␦ T cells are able to provide help for B cell responses. Initial studies performed in mice lacking ␣␤ T cells showed that B cell expansion, differentiation, and secretion of 'T-dependent' antibody isotypes, IgE, and IgG 1 , were all intact in these mice (10). Furthermore, TCR␤ Ϫ/Ϫ mice challenged repeatedly with parasitic infections could produce germinal centers and generate increased antibody production (11). Using a model of pulmonary allergic inflammation, decreased production of IgE and IgG 1 was seen in mice lacking ␥␦ T cells compared with WT mice (12). The ␥␦ T cells have also been shown to directly induce germinal center formation and Ig hypermutation (13). Interestingly, even though the ␥␦ T cells expressing CD4 account for only 5-10% of all ␥␦ cells, it is this subset that appears to be responsible for inducing germinal centers (14). Human ␥␦ T cells have also been found in germinal centers; these cells were found to up-regulate B cell costimulatory molecules such as CD40L, OX40, CD70, and inducible costimulatory molecule (ICOS) in response to TCR stimulation (15, 16). Together, these data indicate that ␥␦ T cells can promote, either directly or indirectly, th...

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“…2 cd T cells expressing different Vcs have different effects on the immune responses. 8 Recent studies revealed a correlation between TCR-Vc expression and functional differentiation, 9,10 thus emphasizing the biological significance of the cd TCR segregation in the mouse. Nevertheless, specific evidence concerned with IL-17 producing cd T cells suggests that, at least in this case, the correlation between cd TCR expression and function is merely coincidental-waves of cd T cells expressing certain TCRs coincide with a thymic environment that temporarily favors TH17 differentiation.…”

Section: The CD T-cell Receptorsmentioning

confidence: 99%

Diversity of γδ T-cell antigens

2012

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In the last two decades, it has become clear that cd T cells recognize a diverse array of antigens including self and foreign, large and small, and peptidic and non-peptidic molecules. In this respect, cd antigens as a whole resemble more the antigens recognized by antibodies than those recognized by ab T cells. Because of this antigenic diversity, no single mechanism-such as the major histocompatibility complex (MHC) restriction of ab T cells-is likely to provide a basis for all observed T-cell antigen receptor (TCR)-dependent cd T-cell responses. Furthermore, available evidence suggests that many individual cd T cells are poly-specific, probably using different modes of ligand recognition in their responses to unrelated antigens. While posing a unique challenge in the maintenance of self-tolerance, this broad reactivity pattern might enable multiple overlapping uses of cd T-cell populations, and thus generate a more efficient immune response.

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γδ T‐cell receptors: functional correlations

Cited by 92 publications

References 94 publications

Clonal expansion of Epstein–Barr virus (EBV)-infected γδ T cells in patients with chronic active EBV disease and hydroa vacciniforme-like eruptions

Clonal expansion of Epstein–Barr virus (EBV)-infected γδ T cells in patients with chronic active EBV disease and hydroa vacciniforme-like eruptions

Tec kinase Itk in γδT cells is pivotal for controlling IgE production in vivo

Diversity of γδ T-cell antigens

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