A programmed functional and phenotypic development of bone marrow-derived cytotoxic cell precursors in vitro.

An analysis of function and marker expression during cytotoxic cell differentiation in vitro from T cell-depleted bone marrow precursors is described. Cytotoxic activity is not detectable during the first five days of culture, but rises abruptly soon after. Antibody plus complement depletion studies show that cytotoxic cells derive from Thy-1-negative precursors and undergo a continual increase in Thy-1 and Lyt-2 marker expression as the culture progresses. A reciprocal decrease in asialo-GM1 antigen expression on effector cells is seen. The J11d-negative precursor cells acquire J11d (an antigen known to mark cortical thymocytes) at an intermediate stage of culture, but revert to the J11d-negative phenotype prior to functional acquisition. At least some effectors are T cell receptor positive as illustrated by an anti-T cell receptor antibody-mediated killing assay. These patterns precisely correlate with those detected among developing T cells in vivo. Results may indicate that a programmed course of differentiation inherent to bone marrow cells may be triggered in the absence of a thymic environment.