REGULATION OF CD4 AND CD8 EXPRESSION ON MOUSE T-CELLS - ACTIVE REMOVAL FROM THE CELL-SURFACE BY 2 MECHANISMS

Phorbol esters are known to induce a loss of CD4 from the surface of m ouse and human T cells, presumably through activation of protein kinas e C. Here we describe additional, calcium-dependent processes that rem ove CD4 and CD8 from the surface of T cells and thymocytes, and that d iffer from the protein kinase C-mediated effect in that they require t he expression of new gene products. Whereas PMA causes the disappearan ce of almost all CD4 from the surface of mouse CD4+8+ thymocytes, it i nduces only a partial (approximately 60%) and transient (10 to 12 h) l oss of CD4 from the surface of mouse peripheral T cells, with no effec t on CD8 expression. When T cells are exposed to a combination of PMA and the calcium ionophore, ionomycin (CaI), surface CD4 virtually disa ppears for a period of at least 24 h, and CD8 expression is also dimin ished. This additional, calcium-dependent effect, on both CD4 and CD8 expression, is abrogated by either cycloheximide or actinomycin D, and so depends on new RNA and protein synthesis. There appear, therefore, to be two distinct mechanisms for the removal of CD4 and CD8 from mou se peripheral T cells: one induced by PMA alone, the second by the com bination of PMA and CaI. The second mechanism, but not the first, depe nds on the expression of new gene products. In contrast to mouse perip heral T cells, mouse thymocytes and human peripheral blood T cells res pond to PMA alone with virtually a complete loss of surface CD4, and p artial loss of CD8 expression. The addition of CaI has no synergistic effect on CD4 expression in either of these populations, but augments the loss of CD8 in mouse thymocytes.