The in vivo immunosuppressive action of suppressor cells from alloantigen-cyclosporine-treated mice and the capacity of spleen cells to release interleukins and gamma-interferon.

Abstract

Antigen-nonspecific suppressor T cells were identified in spleens of mice rendered unresponsive by sensitization of allogeneic antigen in combination with cyclosporine (CsA) treatment. Suppressor cells were obtained from C57BL/6 (B6, H-2b) mice treated with a single i.p. injection of 1 x 10(7) allogeneic P815 (H-2d) cells combined with a five-day course of CsA, a group that did not show any cytotoxic activity of spleen cells against P815 targets. These noncytolytic spleen cells displayed suppressor activity on the induction of cytotoxic T (Tc) cells of normal lymphocytes against not only P815 stimulator (80.9% suppression, P less than 0.01, responder:additional cell ratio = 2.5:1) but also third-party BW5147 (H-2k) stimulator (68.2% suppression, P less than 0.01). The unresponsive state appears to be due to suppressor T (Ts) cells that are nonadherent to plastic or nylon-wool, 1500 rads-sensitive, and Thy-1-positive. Capacities of spleen cells from CsA-P815-treated mice to release cytokines (interleukin 1 [IL-1]), interleukin 2 [IL-2], interleukin 3 [IL-3], and gamma-interferon [gamma-IFN]) were examined. Spleen cells from CsA-P815-treated B6 mice displayed 84.1%, 91.7% and 90.8% inhibition (0.35 +/- 0.07 U/ml, 1.4 +/- 0.29 U/ml, and 7.0 +/- 0.9 U/ml) of IL-1, IL-2, and gamma-IFN production compared with normal mice (2.2 +/- 0.54 U/ml, 16.9 +/- 2.1 U/ml, and 76.0 +/- 3.1 U/ml, P less than 0.01), respectively. However, IL-3 production was significantly less inhibition (46.1%, 2.35 +/- 1.0 U/ml in CsA-P815-treated mice and 4.36 +/- 1.7 U/ml in normal mice) compared with other cytokines (IL-1, IL-2, gamma-IFN). Two systems were employed to assess the immunosuppressive efficacy of antigen-nonspecific Ts cells in vivo. First, adoptive transfer (i.p.) of spleen cells harvested from CsA-P815-treated mice ten days after treatment on 3 consecutive days (days 0, 1, 2) at a 3 x 10(7) cell dose into virgin B6 mice that were immunized with P815 cells (1 x 10(7), day 0) completely inhibited the development of Tc cells against P815 targets (5% specific cytolysis, effector:target ratio [E:T] = 200). The suppressor effect was immunologically nonspecific; adoptive transfer of Ts cells from CsA-P815-treated mice also abrogated the development of Tc cells against third=party BW5147 cells.(ABSTRACT TRUNCATED AT 400 WORDS)