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

(110 citation statements)

References 94 publications

(103 reference statements)

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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%

See 1 more Smart Citation

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.

113

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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“…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%

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.

113

145

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show abstract

“…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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“…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

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

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

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

Diversity of γδ T-cell antigens

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