Cyclosporin A blocks the generation of alloindifferent but not of allospecific suppressive cells

Abstract

The induction of alloantigen-indifferent, MHC unrestricted suppressive cells (SC) early on in human mixed lymphocyte culture (MLC) or after stimulation with suppressive T cell clones was blocked in a dose-dependent fashion by cyclosporin A (CsA). This was not prevented by the addition of the following defined lymphokines: interleukin (IL) -1, -2, -4, -5, interferon-tau or GM-CSF. The addition of MLC-conditioned medium as a source of multiple lymphokines including IL-3 also failed to reconstitute suppressive activity in the presence of CsA. In contrast, the development of allospecific, HLA-restricted SC in the same CsA-blocked MLC was not prevented or was even enhanced. These results confirm that CsA 'spares' specific SC induction late in MLC, but show that it prevents induction of non-specific suppression earlier in MLC by a mechanism presumably unrelated to blocking the secretion of interferon-tau or IL-1 to IL-5.