SOLUBLE FACTORS SECRETED BY ACTIVATED T-LYMPHOCYTES MODULATE THE TRANSCRIPTION OF THE IMMUNOSUPPRESSIVE CYTOKINE TGF-BETA-2 IN GLIAL-CELLS

Coordination of the immune response to injury or disease in the brain is postulated to involve bi-directional discourse between the immune s ystem and the central nervous system. This cross communication involve s soluble mediators, including various growth factors, cytokines, and neuropeptides. In this report, we demonstrate that the supernatant fro m activated T-lymphocytes is able to induce the transcription of a pot ent cytokine, TGF-beta 2 in glial cells. The activating stimulus invok es signaling mechanisms distinct from known kinase or protease pathway s. Activation of TGF-beta 2 transcription correlates with the loss of binding activity for an 80 kDa glial labile repressor protein, GLRP, t o a responsive region within the TGF-beta 2 promoter. Although GLRP sh ares some characteristics with the inducible transcription factor AP-1 , it appears to be distinct from known AP-1 family members. These data along with previous observations demonstrating the potent immunosuppr essive activity of TGF-beta 2, support a model for a feedback mechanis m between the activated T-lymphocytes and astrocytes via TGF-beta 2 to regulate the immune response. (C) 1996 Wiley-Liss, Inc.