Distinct Effects of Jak3 Signaling on αβ and γδ Thymocyte Development
| Autor: | Elizabeth E. Eynon, Ferenc Livák, Keisuke Kuida, David G. Schatz, Richard A. Flavell |
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| Rok vydání: | 1999 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 162:1448-1459 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.162.3.1448 |
| Popis: | Janus kinase 3 (Jak3) plays a central role in the transduction of signals mediated by the IL-2 family of cytokine receptors. Targeted deletion of the murine Jak3 gene results in severe reduction of αβ and complete elimination of γδ lineage thymocytes and NK cells. The developmental blockade appears to be imposed on early thymocyte differentiation and/or expansion. In this study, we show that bcl-2 expression and in vivo survival of immature thymocytes are greatly compromised in Jak3−/− mice. There is no gross deficiency in rearrangements of the TCRδ and certain γ loci in pre-T cells, and a functional γδ TCR transgene cannot rescue γδ lineage differentiation in Jak3−/− mice. In contrast, a TCRβ transgene is partially able to restore αβ thymocyte development. These data suggest that the signals mediated by Jak3 are critical for survival of all thymocyte precursors particularly during TCRβ-chain gene rearrangement, and are continuously required in the γδ lineage. The results also emphasize the fundamentally different requirements for differentiation of the αβ and γδ T cell lineages. |
| Databáze: | OpenAIRE |
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