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Regulation of memory CD4 T-cell pool size and function by natural killer T cells in vivo.


ABSTRACT: To develop more effective vaccines and strategies to regulate chronic inflammatory diseases, it is important to understand the mechanisms of immunological memory. Factors regulating memory CD4(+) T helper (Th)-cell pool size and function remain unclear, however. We show that activation of type I invariant natural killer T (iNKT) cells with glycolipid ligands and activation of type II natural killer T (NKT) cells with the endogenous ligand sulfatide induced dramatic proliferation and expansion of memory, but not naïve, CD4 T cells. NKT cell-induced proliferation of memory Th1 and Th2 cells was dependent largely on the production of IL-2, with Th2-cell proliferation also affected by loss of IL-4. Type II NKT cells were also required for efficient maintenance of memory CD4 T cells in vivo. Activation of iNKT cells resulted in up-regulation of IFN-? expression by memory Th2 cells. These IFN-?-producing memory Th2 cells showed a decreased capability to induce Th2 cytokines and eosinophilic airway inflammation. Thus, activated NKT cells directly regulate memory CD4 T-cell pool size and function via the production of cytokines in vivo.

SUBMITTER: Iwamura C 

PROVIDER: S-EPMC3479525 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Regulation of memory CD4 T-cell pool size and function by natural killer T cells in vivo.

Iwamura Chiaki C   Shinoda Kenta K   Endo Yusuke Y   Watanabe Yukiko Y   Tumes Damon John DJ   Motohashi Shinichiro S   Kawahara Kazuyoshi K   Kinjo Yuki Y   Nakayama Toshinori T  

Proceedings of the National Academy of Sciences of the United States of America 20121001 42


To develop more effective vaccines and strategies to regulate chronic inflammatory diseases, it is important to understand the mechanisms of immunological memory. Factors regulating memory CD4(+) T helper (Th)-cell pool size and function remain unclear, however. We show that activation of type I invariant natural killer T (iNKT) cells with glycolipid ligands and activation of type II natural killer T (NKT) cells with the endogenous ligand sulfatide induced dramatic proliferation and expansion of  ...[more]

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