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The SLAM-associated protein signaling pathway is required for development of CD4+ T cells selected by homotypic thymocyte interaction.


ABSTRACT: MHC class II-expressing double-positive thymocytes induce progression of CD4(+) T cell development as efficiently as cortical thymic epithelial cells do. Because double-positive thymocytes expressing CD1d select natural killer T (NKT) cells, we investigated whether thymocyte-selected CD4(+) (T-CD4) T cells require the same signaling components as NKT cells. Using bone-marrow chimeras, we found that the signaling molecules SAP, Fyn, and PKCtheta were essential for T-CD4 T cell generation, whereas mutations in the Ly108 receptor, interleukin-15 receptor alpha, or the transcription factor T-bet had a marginal effect. Furthermore, SAP was critical for IL-4 production by T-CD4 T cells, but the PKCtheta deficiency did not alter the ability of T-CD4 T cells to produce cytokines. T-bet was necessary to produce the maximum amount of IFN-gamma for CD4(+) T cells regardless of the selection pathway. Thus, in contrast to epithelial cell-selected CD4(+) T cells, the two distinct lineages of T cells selected by thymocytes--i.e., T-CD4 and NKT cells--both utilize the SAP-Fyn-PKCtheta pathway for their development and function.

SUBMITTER: Li W 

PROVIDER: S-EPMC2757291 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature

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The SLAM-associated protein signaling pathway is required for development of CD4+ T cells selected by homotypic thymocyte interaction.

Li Wei W   Sofi M Hanief MH   Rietdijk Svend S   Wang Ninghai N   Terhorst Cox C   Chang Cheong-Hee CH  

Immunity 20071101 5


MHC class II-expressing double-positive thymocytes induce progression of CD4(+) T cell development as efficiently as cortical thymic epithelial cells do. Because double-positive thymocytes expressing CD1d select natural killer T (NKT) cells, we investigated whether thymocyte-selected CD4(+) (T-CD4) T cells require the same signaling components as NKT cells. Using bone-marrow chimeras, we found that the signaling molecules SAP, Fyn, and PKCtheta were essential for T-CD4 T cell generation, whereas  ...[more]

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