Antigen-specific suppression of antibody responses by T lymphocytes cytotoxic for antigen-presenting cells

Abstract

In this study we demonstrated an alternative model of the antigen (Ag)-specific suppression of antibody response in mice. Splenocytes that were taken from BALB/c mice immunized by i.v. injection of soluble human serum albumin (HSA) or ovalbumin exhibited MHC-restricted Ag-specific cytotoxicity for the respective antigen-presenting cells (APC). When HSA-primed splenocytes cultured with Ag and interleukin-2 (IL-2) were treated with anti-CD4 or anti-CD8 monoclonal antibody (mAb) plus complement, CD8+ and CD4+ T cells exhibited nearly the same level of cytotoxicity against APC. Furthermore, HSA-primed CD4+ and CD8+ T cells released the same amount of interferon-gamma (IFN-gamma) when stimulated with Ag and IL-2. Recombinant IFN-gamma was shown to suppress the in vitro plaque-forming cell (PFC) response to sheep red blood cells (SRBC) only when it was added within 24 h after addition of Ag. The supernatants from both HSA-primed CD4+ and CD8+ T cells suppressed the PFC response to SRBC in vitro, and the suppressive activity was abrogated by anti-IFN-gamma mAb, but increased by anti-IL 4 mAb. These results suggest that in our system the effector cells for Ag-specific suppression of the antibody response in mice are both the cytotoxic type 1 clones (IFN-gamma-producing) of CD4+ and CD8+ T cells for APC, and that IFN-gamma is a major extracellular effector molecule for such suppression.