TGF-β suppresses antigen stimulation of a uveitogenic t cell line through an effect on antigen-presenting cells

TGF-β is thought to have a central role in the control of cell-mediated autoimmunity. We wished to examine the effect of TGF- β on stimulation of the uveitogenic rat T cell line SP35, specific to peptide 35 of the retinal S-Antigen. SP35 cells were stimulated through the T cell receptor (TCR) in the presence or absence of TGF-β1 by one of two methods: peptide presented on syngeneic antigen-presenting cells (APC) or crosslinking of CD3 plus CD28 engagement by specific monoclonal antibodies. TGF- β1 concentrations r 0.15 ng/ml reproducibly suppressed antigen/APC-driven proliferation of SP35 cells by up to 50% in a dose-dependent fashion. The level of suppression appeared to remain constant over a range of APC concentrations from 1×105 to 5×105 cells/well and TGF-β concentrations beteween 1 and 10 ng/ml. In contrast, no suppression was seen when SP35 cells were stimulated by anti-CD3/antiCD28, even at a TGF-β concentration 60-fold greater than that needed to suppress antigen-driven proliferation. We conclude that TGF-β1 can partially suppress the response of uveitogenic SP35 line cells to TCR-mediated stimulation. The inhibition seems to be exerted at the level of the APC since stimulation by monoclonal antibodies was not suppressed. The suppression plateaued at 30-50%, suggesting a selective effect on a noncritical APC function(s). We believe that additional mechanisms to inhibition of antigenic stimulation of pathogenic effector T cells must be invoked to explain the central role attributed to TGF-β in the control of cell- mediated autoimmunity m vivo .

Duke Scholars

Author Teresa Kathleen Tarrant Medicine, Rheumatology and Immunology