Suppression of mixed lymphocyte reactivity by murine bone-marrow-derived suppressor factor--inhibition of proliferation due to a deficit in IL-2 production.

Murine bone marrow natural suppressor cells constitutively produce a soluble factor, BDSF, that suppresses murine Ab responses in vitro. BDSF is recovered in supernatants of cultured BM cells and resides in an MW range between 1-10 kD. We now demonstrate that BDSF suppresses proliferation in the mixed lymphocyte reaction (MLR). In order to elucidate the potential mechanism of action, BDSF was tested for the ability to interfere with IL-2-mediated T cell proliferation. BDSF was not able to inhibit IL-2-driven proliferation of the cell lines CTLL-2 and HT-2. However, examination of MLR culture supernatants revealed that suppression of proliferation by BDSF was associated with decreased levels of IL-2 production. Furthermore, responsiveness of BDSF-treated cultures could be reconstituted by adding exogenous IL-2, at the time of plating. The results suggest that hyporesponsiveness in the presence of BDSF is due to a deficit in IL-2 production, preventing expansion of Ag-stimulated cells.