Soluble suppressive molecule released by human T lymphocytes induced by heat-inactivated allostimulator cells in the presence of cyclosporine.

ABSTRACT

E-rosette-positive peripheral blood lymphocytes (E+PBL) stimulated initially with heat-inactivated allogeneic lymphoblastoid cells in the presence of cyclosporine (CsA/HI) produce a soluble molecule that suppresses fresh lymphocytes in a primary mixed lymphocyte reaction. Cell lines were derived from the E+PBL cells after one and two weeks of culture. These lines were CD4+ by both FACS and mRNA analysis. The cells produce a potent soluble molecule (supernates often containing greater than 1000 units of suppressive activity per milliliter). The factor has an apparent molecular weight of 90 k and is sensitive to both pH and boiling. The molecule is not the suppressive cytokine TGF beta, based on neutralization with anti-TGF beta antibody and mRNA expression. None of the available cytokines expressed by these cells was suppressive when titrated into an MLR, alone or in combination. These results support the conclusion that CsA/HI-activated T cell lines produce a novel cytokine that is not antigen-specific or MHC-restricted.