Distinct T lymphocyte subsets affect granulo-monocytic differentiation and proliferation

Bone marrow culture techniques using semi-solid support-media provide an opportunity to observe granulocyte-macrophage progenitor cells proliferating and differentiating in vitro. Cells from the bone marrow and peripheral blood produce specific growth factors which stimulate both the proliferation and differentiation processes (collectively termed colony-stimulating factors or activity, CSF/CSA). Even highly purified CSA induces proliferation and concomitant differentiation suggesting that the two processes are inseparable. We here present evidence to suggest that the two processes are, at least in part, individually regulated. We observed delayed differentiation by morphological, cytochemical and functional criteria in granulocyte-macrophage clones formed in cultures in which the growth stimulus was supplied by marrow or blood cells which have been depleted of T lymphocytes bearing the OKT3/MBG6 antigen(s) by complement lysis. The proliferation stimulus was unaffected. T cell depletion using another monoclonal antibody, OKT11a (which removed an overlapping but not identical population of T cells), did not produce the same effect but did increase the level of CSA produced by the remaining marrow cells. Selective replacement experiments using OKT4+ or OKT8+ cell preparations suggested that removal of an MBG6+, OKT3+, OKT8+, OKT4-lymphocyte subset is responsible for the effect on differentiation.