A model system for T-lymphocyte differentiation: regulation of CD4 and CD8 gene expression in SL12.4 T-lymphoma cell...

The T-cell surface proteins CD4 (L3T4) and CD8 (Lyt2) are first expressed on thymocytes as they undergo maturation in the thymus. Two immature T-lymphoma cell clones SL12.4 and RS4.2 which constitutively express low or undetectable levels of CD4 and CD8 were used to investigate the activation of CD4 and CD8 gene expression. The protein synthesis inhibitors cycloheximide (CHX) and pactamycin rapidly and reversibly increased CD4 and CD8 mRNA in the cloned cell lines, suggesting that a labile inhibitor protein(s) may regulate the expression of these transcripts. Cell surface CD4 and CD8 proteins were transiently detectable following a pulse of CHX. Thymic epithelial cell lines also induced CD4 and CD8 mRNA and cell surface protein, as well as TCR-alpha mRNA when co-cultivated with SL12.4 T lymphoma cells. The increase in CD4 and CD8 was modest, but stable for at least 22 cell generations after the thymic epithelial inducer cells were removed. Epithelial cells of non-thymic origin did not cause induction of these T-cell differentiation markers in SL12.4 T-lymphoma cells. Since the induction elicited by thymic epithelial cells and protein synthesis inhibitors differed dramatically in kinetics and reversibility, it is likely that these inducers act, at least in part, via different mechanisms. This lymphoma model system may be useful for analysis of molecular events which occur in immature thymocytes undergoing differentiation.