The CD4 surface antigen is induced and maintained on a T-lymphoid cell line by tumor necrosis factor-alpha.

We have used the L4E murine thymoma-derived T-lymphoid cell line to study mechanisms involved in CD4 expression. When L4E cells are cocultured with the St3 stromal cell line, surface CD4 expression is maintained, even across a membrane. However, when transferred to medium alone, these cells rapidly lose CD4. We have tested whether CD4 can be maintained on CD4+ L4E cells when they are transferred to medium containing known cytokines. In these results, rmTNF-alpha maintained surface CD4 expression at significant levels on L4E cells. In addition, rmTNF-alpha could induce CD4 on CD4- L4E cells (obtained by growth in medium alone). Despite these results CD4 induction and maintenance in L4E cells by coculture with St3 stroma did not appear to result from secretion of TNF-alpha, since St3 cells did not express TNF-alpha mRNA, secreted TNF-alpha was not detected by ELISA assay in supernatant from St3 cells nor L4E-St3 cocultures, and incubation with neutralizing anti-TNF-alpha antibody did not inhibit CD4 maintenance. The ability of TNF-alpha to affect CD4 expression on L4E cells supports a role in thymocyte differentiation for this cytokine.