SAP regulation of follicular helper CD4 T cell development and humoral immunity is independent of SLAM and Fyn kinase

Megan M. McCausland, Isharat Yusuf, Hung Tran, Nobuyuki Ono, Yusuke Yanagi, Shane Crotty

研究成果: ジャーナルへの寄稿学術誌査読

79 被引用数 (Scopus)

抄録

Mutations in SH2D1A resulting in lack of SLAM-associated protein (SAP) expression cause the human genetic immunodeficiency X-linked lymphoproliferative disease. A severe block in germinal center development and lack of long-term humoral immunity is one of the most prominent phenotypes of SAP- mice. We show, in this study, that the germinal center block is due to an essential requirement for SAP expression in Ag-specific CD4 T cells to develop appropriate follicular helper T cell functions. It is unknown what signaling molecules are involved in regulation of SAP-dependent CD4 T cell help functions. SAP binds to the cytoplasmic tail of SLAM, and we show that SLAM is expressed on resting and activated CD4 T cells, as well as germinal center B cells. In addition, SAP can recruit Fyn kinase to SLAM. We have now examined the role(s) of the SLAM-SAP-Fyn signaling axis in in vivo CD4 T cell function and germinal center development. We observed normal germinal center development, long-lived plasma cell development, and Ab responses in SLAM-/- mice after a viral infection (lymphocytic choriomeningitis virus). In a separate series of experiments, we show that SAP is absolutely required in CD4 T cells to drive germinal center development, and that requirement does not depend on SAP-Fyn interactions, because CD4 T cells expressing SAP R78A are capable of supporting normal germinal center development. Therefore, a distinct SAP signaling pathway regulates follicular helper CD4 T cell differentiation, separate from the SLAM-SAP-Fyn signaling pathway regulating Th1/Th2 differentiation.

本文言語英語
ページ(範囲)817-828
ページ数12
ジャーナルJournal of Immunology
178
2
DOI
出版ステータス出版済み - 1月 15 2007

!!!All Science Journal Classification (ASJC) codes

  • 免疫アレルギー学
  • 免疫学

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