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The Role Of IGF System In Lymphocytes Activation
Author(s) -
Idelman Gila,
De Siervi Adriana,
Haggerty Cynthia M,
Montano Idalia,
Taub Dennis D,
Gardner Kevin
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a252-d
Subject(s) - cd28 , cytotoxic t cell , microbiology and biotechnology , t cell , immune system , protein kinase b , mapk/erk pathway , t cell receptor , cd8 , biology , cancer research , signal transduction , chemistry , immunology , biochemistry , in vitro
The process of T‐cell costimulation is a critical process in the immune response. Classically it involves the activation of cell surface molecules that alone are incapable of activating T‐cells but modify signals generated by the T‐cell Receptor (TCR). In this study we provide novel evidence that insulin growth factor‐1 (IGF‐1) and its receptor (IGF‐IR) represent a true costimulatory system in human T‐cells. We show a significant costimulation effect of IGF on the proliferation of both mouse splenocytes and human T‐cells. This response is functionally associated with increased IL‐2 production, cell survival and cytotoxic T‐lymphocyte killing. Major intracellular targets for IGF‐1‐TCR synergistic action include Akt, ERK, NF‐kappa B and CREB. Finally we show for the first time that the lymphoid oncogene TPL2 is an important target for IGF‐1 in activated T‐cells. Moreover, we propose that TPL2 is a key regulator of a feedforward network motif that provides sustained signaling during T‐cell activation. In conclusion, our data demonstrate a close involvement of the IGF‐I/IGF‐IR axis in T‐cell homeostasis and tumor progression and provide new insights into the role of IGF‐1 in the regulation of immune function. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute and National Institute on Aging.