Cellular target of in vitro-induced suppressor cells derived from the spleen of Mycobacterium lepraemurium-infected mice and role of IFN-gamma in their development.

Unfractionated spleen cells from C3H mice infected a few weeks before with Mycobacterium lepraemurium developed a suppressor activity after overnight culture. This requires contact of plastic adherent cells with nonadherent cells distinct from T, B, or natural killer cells. The present study demonstrates that anti-interferon-gamma (IFN-gamma) monoclonal antibody and indomethacin totally abrogate the expression, although not the induction, of this activity. Furthermore, culture-induced suppressor cells selectively inhibit T lymphocyte proliferation, probably by altering the generation of interleukin-2 (IL-2) responsiveness through reduction of the affinity and density of high-affinity IL-2 receptors on activated cells. These and other previously determined properties of culture-induced suppressor cells, similar to those of adherent suppressor cells detected in freshly harvested spleen cells at a later stage of M. lepraemurium infection, suggest a common precursor. If so, the present observations should help in defining a strategy to prevent the impairment of cell-mediated immunity in infected mice.