| First Author | Chen Y | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 1 | Pages | 61-71 |
| PubMed ID | 22623331 | Mgi Jnum | J:188956 |
| Mgi Id | MGI:5442664 | Doi | 10.4049/jimmunol.1103272 |
| Citation | Chen Y, et al. (2012) Differential requirement of RasGRP1 for gammadelta T cell development and activation. J Immunol 189(1):61-71 |
| abstractText | gammadelta T (gammadeltaT) cells belong to a distinct T cell lineage that performs immune functions different from alphabeta T (alphabetaT) cells. Previous studies established that Erk1/2 MAPKs are critical for positive selection of alphabetaT cells. Additional evidence suggests that increased Erk1/2 activity promotes gammadeltaT cell generation. RasGRP1, a guanine nucleotide-releasing factor for Ras, plays an important role in positive selection of alphabetaT cells by activating the Ras-Erk1/2 pathway. In this article, we demonstrate that RasGRP1 is critical for TCR-induced Erk1/2 activation in gammadeltaT cells, but it exerts different roles for gammadeltaT cell generation and activation. Deficiency of RasGRP1 does not obviously affect gammadeltaT cell numbers in the thymus, but it leads to increased gammadeltaT cells, particularly CD4(-)CD8(+) gammadeltaT cells, in the peripheral lymphoid organs. The virtually unhindered gammadeltaT cell development in the RasGRP1(-/-) thymus proved to be cell intrinsic, whereas the increase in CD8(+) gammadeltaT cells is caused by non-cell-intrinsic mechanisms. Our data provide genetic evidence that decreased Erk1/2 activation in the absence of RasGRP1 is compatible with gammadeltaT cell generation. Although RasGRP1 is dispensable for gammadeltaT cell generation, RasGRP1-deficient gammadeltaT cells are defective in proliferation following TCR stimulation. Additionally, RasGRP1-deficient gammadeltaT cells are impaired to produce IL-17 but not IFNgamma. Together, these observations revealed that RasGRP1 plays differential roles for gammadelta and alphabeta T cell development but is critical for gammadeltaT cell proliferation and production of IL-17. |
