GADD45β and GADD45γ have previously been shown to be crucial for the initiation of T helper 1 (TH1)-cell immune responses and this has been attributed to their effect on p38-mitogen-activated protein kinase. However, in other cell types, they have a role in regulating cell-cycle progression and cell death; so, Liu et al. set out to investigate the role of GADD45β in regulating T-cell proliferation. Following stimulation through the T-cell receptor, GADD45β-deficient T cells underwent more rounds of cell division than GADD45β-sufficient control T cells. Similarly, when stimulated with interleukin-12 (IL-12) and IL-18, GADD45β-deficient TH1 cells divided more times than control cells. In addition, GADD45β-deficient TH1 cells showed increased resistance to activation-induced cell death (AICD).
Consistent with a role for GADD45β in controlling T-cell proliferation and susceptibility to AICD, GADD45β-deficient mice were more susceptible than control mice to experimental autoimmune encephalomyelitis (EAE). This increase in disease was caused by a T-cell defect because recombination-activating gene 1 (RAG1)-deficient recipients of GADD45β-deficient CD4+ T cells were also more susceptible to disease than recipients of wild-type control cells; and it was associated with TH1-cell infiltration of the central nervous system.
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