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Publication : Critical role of TCR specificity in the development of Vγ1Vδ6.3+ innate NKTγδ cells.

First Author  Pereira P Year  2013
Journal  J Immunol Volume  191
Issue  4 Pages  1716-23
PubMed ID  23851687 Mgi Jnum  J:205694
Mgi Id  MGI:5546265 Doi  10.4049/jimmunol.1203168
Citation  Pereira P, et al. (2013) Critical role of TCR specificity in the development of Vgamma1Vdelta6.3+ innate NKTgammadelta cells. J Immunol 191(4):1716-23
abstractText  A large fraction of innate NKTgammadelta T cells uses TCRs composed of a semi-invariant Vdelta6.3/6.4-Ddelta2-Jdelta1 chain together with more diverse Vgamma1-Jgamma4 chains. To address the role of gammadeltaTCR specificity in their generation, we analyzed their development in mice transgenic (Tg) for a Vgamma1-Jgamma4 chain frequently expressed by NKTgammadelta cells (Tg-gamma) and in mice Tg for the same Vgamma1-Jgamma4 chain together with a Vdelta6BDdelta2Jdelta1 chain not usually found among NKTgammadelta cells (Tg-gammadelta). Surprisingly, both promyelocytic leukemia zinc finger (PLZF)(+) and NK1.1(+) NKTgammadelta cells were found in the thymus of Tg-gammadelta albeit at lower numbers than in Tg-gamma mice, and virtually all of them expressed the Tg TCR. However, the PLZF(+) subset, but not the NK1.1(+) subset, also expressed an endogenous Vdelta6.3/6.4 chain, and its size was severely reduced in TCRdelta(-/-) Tg-gammadelta mice. These results could suggest that the PLZF(+) and the NK1.1(+) subsets are developmentally unrelated. However, PLZF(+) and NK1.1(+) NKTgammadelta cells express identical Vdelta6.3/6.4 chains, and NK1.1(+) cells can be obtained upon intrathymic injection of sorted PLZF(+) cells, thus indicating their developmental relationship. In fact, the NK1.1(+) gammadelta thymocytes present in Tg-gammadelta mice correspond to a small subset of NK1.1(+) gammadelta thymocytes in wild-type animals, which express a more diverse repertoire of TCRs and can be recognized by the expression of the CD62L Ag. Collectively, our data demonstrated that TCR specificity is essential for the development of most NKTgammadelta T cells and revealed a developmental heterogeneity in gammadelta T cells expressing the NK1.1 marker.
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