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Activation of NF‐kB1 by OX40 contributes to antigen‐driven T cell expansion and survival
Author(s) -
Song Jianxun,
So Takanori,
Croft Michael
Publication year - 2008
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.22.1_supplement.662.5
Subject(s) - microbiology and biotechnology , biology , t cell , signal transduction , survivin , cell growth , antigen , cancer research , nf κb , intracellular , apoptosis , immune system , immunology , genetics
The costimulatory molecule OX40 (CD134) is strongly required in many instances for effective T cell‐mediated immunity, controlling proliferation and survival of T cells after encountering specific antigen. We previously found that the functional targets of OX40 are survivin and aurora B that regulate proliferation, and Bcl‐2 anti‐apoptotic family members that regulate survival. However, the intracellular pathways from OX40 that mediate these effects are unclear. Here, we show that OX40 signaling can target the canonical NF‐kB (NF‐kB1) pathway in peripheral antigen‐responding CD4 T cells. Phosphorylation of IkBalpha which leads to NF‐kB1 (p50)/RelA nuclear translocation is impaired in OX40‐deficient T cells. Retroviral transduction of active IKKbeta that constitutively activates NF‐kB1 rescues the poor proliferation and survival of OX40‐deficient T cells, directly correlating with increased expression and activity of survivin, aurora B, and Bcl‐2 family members. Moreover, active IKKbeta expression alone is sufficient to restore the defective proliferation and survival of OX40‐deficient T cells in vivo when responding to antigen. Thus, OX40 signals regulate T cell number and viability through the NF‐kB1 pathway that controls expression and activity of intracellular targets for proliferation and survival.