SLAT regulates CD8+ T cell clonal expansion in a Cdc42- and NFAT1-dependent manner.
SLAT regulates CD8+ T cell clonal expansion in a Cdc42- and NFAT1-dependent manner.
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DOI：
10.4049/jimmunol.1201685
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发表时间：
2013-01-01
期刊：
影响因子：
--
通讯作者：
Bécart S
中科院分区：
文献类型：
--
作者：
Feau S;Schoenberger SP;Altman A;Bécart S
Following antigenic stimulation, CD8+ T cells undergo clonal expansion and differentiation into cytotoxic T lymphocytes (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 that plays a role in CD4+ T cell activation and T-helper cell differentiation by controlling Ca2+/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 ascribe a new and pivotal role to SLAT-mediated NFAT activation in CD8+ T cells, providing new insight into the signaling pathways involved in CD8+ T cell proliferation.
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影响因子：
64.5
作者：
Kaech, SM;Hemby, S;Ahmed, R
通讯作者：
Ahmed, R
影响因子：
15.9
作者：
Becart, Stephane;Charvet, Celine;Altman, Amnon
通讯作者：
Altman, Amnon
影响因子：
4.4
作者：
Leung-Theung-Long, Stephane;Mondor, Isabelle;Guerder, Sylvie
通讯作者：
Guerder, Sylvie
DOI：
10.4049/jimmunol.0902573
发表时间：
2009-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Canonigo-Balancio AJ;Fos C;Prod'homme T;Bécart S;Altman A
通讯作者：
Altman A
DOI：
10.1073/pnas.1004661107
发表时间：
2010-07-06
影响因子：
11.1
作者：
Pham, Nhat-Long L.;Pewe, Lecia L.;Harty, John T.
通讯作者：
Harty, John T.