| First Author | Feau S | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 1 | Pages | 174-83 |
| PubMed ID | 23197258 | Mgi Jnum | J:190836 |
| Mgi Id | MGI:5449778 | Doi | 10.4049/jimmunol.1201685 |
| Citation | Feau S, et al. (2013) SLAT Regulates CD8+ T Cell Clonal Expansion in a Cdc42- and NFAT1-Dependent Manner. J Immunol 190(1):174-83 |
| abstractText | After antigenic stimulation, CD8(+) T cells undergo clonal expansion and differentiation into CTLs that can mount a strong defense against intracellular pathogens and tumors. SWAP-70-like adapter of T cells (SLAT), also known as Def6, is a novel guanine nucleotide exchange factor for the Cdc42 GTPase and plays a role in CD4(+) T cell activation and Th cell differentiation by controlling Ca(2+)/NFAT signaling, but its requirement in CD8(+) T cell response has not been explored. Using a range of transgenic and knockout in vivo systems, we show that SLAT is required for efficient expansion of CD8(+) T cells during the primary response but is not necessary for CTL differentiation. The reduced clonal expansion observed in the absence of SLAT resulted from a CD8(+) T cell-intrinsic proliferation defect and a reduced IL-2-dependent cell survival. On a molecular level, we show that Def6 deficiency resulted in defective TCR/CD28-induced NFAT translocation to the nucleus in CD8(+) T cells. Constitutively active Cdc42 or NFAT1 mutants fully restored the impaired expansion of Def6(-/-) CD8(+) T cells. Taken together, these data describe a new and pivotal role of SLAT-mediated NFAT activation in CD8(+) T cells, providing new insight into the signaling pathways involved in CD8(+) T cell proliferation. |
