NGFI-A gene expression is necessary for T lymphocyte proliferation.

NGFI-A is an immediate early gene, encoding a zinc finger protein, rapidly activated after mitogenic stimulation. NGFI-A gene expression was found to be rapidly and transiently induced after interleukin-2 (IL-2) stimulation of G1 lymphoblasts, as well as during the G0/G1 transition, when stimulated with concanavalin A (ConA). Activation of both Ca2+ and protein kinase C pathways, separately, in quiescent T lymphocytes produced a partial induction of this gene; however, both stimuli together are necessary to obtain a full response. ConA-induced activation of NGFI-A in quiescent cells was inhibited by immunosuppressors. 8-Bromo-cAMP was able to inhibit the expression of this gene in G1 lymphoblasts after IL-2 stimulation, but failed to interfere with the ConA-induced expression in quiescent T lymphocytes. Exposure of T cells to an NGFI-A antisense oligonucleotide blocked the ConA- and IL-2-induced proliferation of the cells, measured as thymidine incorporation and cell number. This inhibition provides direct evidence that the early gene NGFI-A plays a regulatory role in growth control processes of lymphocytes and that its expression is essential for cellular proliferation.