Selective inhibition of the generation of T suppressor cells of contact sensitivity in vitro by interferon

Abstract

The T suppressor (Ts) cell response in contact sensitivity is preferentially inhibited by murine interferon-alpha, beta (IFN-alpha, beta) in vivo. Previous studies in vivo have suggested that IFN exerts its effect directly on the Ts subpopulation rather than through an effect on antigen-presenting macrophages. Nevertheless, the mechanism of this selective blockade remained unclear. To better define the mechanism(s) of inhibition of suppression by IFN-alpha, beta, we determined whether IFN acted on lymphocytes, macrophages, or both. Antigen-specific T effector cells of delayed-type hypersensitivity (TDH) and Ts cells were induced in vitro by co-culture of spleen lymphocytes with bone marrow-derived antigen-presenting macrophages (BM-MA) pulse-labeled with 2,4-dinitrobenzene sulfonate (DNBSO3). TDH or Ts activity was demonstrated by transfer of the lymphocytes into naive recipient BALB/c mice after 3 days of culture. BM-MA cultured for 5 to 7 days (BM-MA d5-7) before labeling preferentially activated TDH cells (Thy-1+, Lyt-1+2-); 10- to 14-day-old BM-MA (BM-MA d10) induced Ts cells (Thy-1+, Lyt-2+), as previously shown. Treatment of the spleen lymphocyte suspension with pure mouse IFN-alpha, beta at a dose of 10(3) U/10(8) cells completely blocked the induction of Ts cells but had no effect on the induction of TDH cells. Pretreatment of the antigen-presenting BM-MA for 24 hr with IFN (10(2) U/3 X 10(5) cells) had no effect on the induction of Ts and TDH cells. Cultivation of lymphocytes on a DNP-BM-MA d6 monolayer did not result in the induction of Ts cells; however, in the presence of a goat anti-murine IFN-alpha, beta antibody, Ts cells were induced. This finding indicates that the spontaneous release of IFN-alpha, beta in those cultures prevented the induction of Ts cells. These results confirm our previous observation that Ts cells are more easily blocked by IFN-alpha, beta than TDH cells, and demonstrate that IFN affects the Ts subpopulation not via modulation of the antigen-presenting macrophages. IFN-alpha, beta-producing, antigen-presenting, or accessory cells may therefore prevent the activation of this type of Ts cell.