Phorbol Ester Induces Changes in the Pattern of Cell Surface Molecules Involved in CTL-Target Cell Interaction

Abstract

Antigen recognition by cytotoxic T lymphocytes (CTLs) is mediated via cell surface molecules (1,2). These involve the T3 molecular complex and the T4, T8, and T11 antigens. Phorbol esters induce a variety of phenotypic changes in lymphocytes, e.g., increased expression of the receptor for interleukin-2 (IL-2) and temporary down-modulation of the T3 receptor complex (3). These phenotypic changes are paralleled by an increased sensitivity to IL-2 and a temporary unresponsiveness to antigen (3). To further characterize the functional changes which accompany the alterations in phenotype we monitored the phorbol ester-induced antigenic changes of cytotoxic T cells defined by monoclonal antibodies to the T11, T8, and T3 molecules and correlated them with the functional changes which occur after phorbol ester stimulation. It was found that after treatment with this most potent tumor promoter—phorbol ester, 12-O-tetra-decanoylphorbol-13-acetate (TPA)—the amount of T3, T4, and T8 molecules decreased on the cell surface while T11 increased. These phenotypic changes are paralleled by temporary loss of cytotoxic activity.