| First Author | Gu JJ | Year | 2007 |
| Journal | J Immunol | Volume | 179 |
| Issue | 11 | Pages | 7334-43 |
| PubMed ID | 18025176 | Mgi Jnum | J:154821 |
| Mgi Id | MGI:4399009 | Doi | 10.4049/jimmunol.179.11.7334 |
| Citation | Gu JJ, et al. (2007) Defective T cell development and function in the absence of Abelson kinases. J Immunol 179(11):7334-43 |
| abstractText | Thymocyte proliferation, survival, and differentiation are tightly controlled by signaling from the pre-TCR. In this study, we show for the first time that the Abelson (Abl) kinases regulate proximal signaling downstream of the pre-TCR. Conditional deletion of Abl kinases in thymocytes reveals a cell-autonomous role for these proteins in T cell development. The conditional knockout mice have reduced numbers of thymocytes, exhibit an increase in the percentage of the CD4(-)CD8(-) double-negative population, and are partially blocked in the transition to the CD4(+)CD8(+) double-positive stage. Moreover, the total number of T cells is greatly reduced in the Abl mutant mice, and the null T cells exhibit impaired TCR-induced signaling, proliferation, and cytokine production. Notably, Abl mutant mice are compromised in their ability to produce IFN-positive CD8 T cells and exhibit impaired CD8(+) T cell expansion in vivo upon Listeria monocytogenes infection. Furthermore, Ab production in response to T cell-dependent Ag is severely impaired in the Abl mutant mice. Together these findings reveal cell-autonomous roles for the Abl family kinases in both T cell development and mature T cell function, and show that loss of these kinases specifically in T cells results in compromised immunity. |
