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Publication : IFN-γ-producing and IL-17-producing γδ T cells differentiate at distinct developmental stages in murine fetal thymus.

First Author  Shibata K Year  2014
Journal  J Immunol Volume  192
Issue  5 Pages  2210-8
PubMed ID  24489104 Mgi Jnum  J:209935
Mgi Id  MGI:5568923 Doi  10.4049/jimmunol.1302145
Citation  Shibata K, et al. (2014) IFN-gamma-producing and IL-17-producing gammadelta T cells differentiate at distinct developmental stages in murine fetal thymus. J Immunol 192(5):2210-8
abstractText  gammadelta T cells develop at the double-negative (DN) 2 and DN3 stages and acquire functions to produce IL-17 and IFN-gamma in fetal thymus. However, the relationship between differentiation stages and their functions was unclear. In this study, we found that, although IFN-gamma-producing and IL-17-producing gammadelta T cells developed from DN2 cells, only IFN-gamma-producing gammadelta T cells developed from DN3 cells, indicating the direct generation of IL-17-producing gammadelta T cells from the DN2 stage, not through the DN3 stage. Single-cell analysis revealed that DN2 cells contained heterogeneous gammadelta T cell precursors with or without an ability to develop IL-17 producers. Inactivation of B cell leukemia/lymphoma 11b, a zinc finger transcription factor responsible for transition from early to late stages of DN2 cells, completely abrogated the development of IL-17-producing gammadelta T cells, although a unique subset of IFN-gamma-producing gammadelta T cells expressing a high level of promyelocytic leukemia zinc finger was able to develop. Thus, our results reveal that gammadelta T cells are functionally differentiated to IFN-gamma and IL-17 producers at different developmental stages in fetal thymus.
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