Phosphorylation and down-regulation of CD4 and CD8 in human CTLs and mouse L cells.
The CD4 and CD8 molecules are rapidly phosphorylated following exposure of CD4+ or CD8+ human cytotoxic T lymphocytes (CTL) clones to B-lymphoblastoid cell lines bearing the relevant target alloantigens. Treatment of CD4+ or CD8+ CTL clones with phorbol myristate acetate (PMA), phytohemagglutinin, or mitogenic combinations of CD2-specific antibodies also resulted in CD4 or CD8 phosphorylation. Down-regulation of the surface expression of these molecules could be demonstrated in both CD4+ and CD8+ clones following exposure to the relevant alloantigen or PMA. Parallel experiments were conducted using mouse L cells in which the human CD4 or CD8 antigens were stably expressed. Exposure of these transfectants to PMA induced rapid phosphorylation of the CD4 and CD8 molecules. As in CD4+ CTL clones, rapid modulation of the CD4 antigen could be demonstrated in L cells following PMA treatment. In contrast, there was no demonstrable down-regulation of the CD8 antigen in PMA-treated CD8+ L cell transfectants. These studies demonstrate a significant differential property of the CD4 and CD8 antigens and suggest that down-regulation of the CD8 antigen may require its expression in a T-cell environment and/or the association of CD8 with the T-cell receptor or other T cell-specific molecules.
DiSanto
J P
JP
Effector Lymphocyte Biology Laboratory, Sloan-Kettering Institute for Cancer Research, New York, NY 10021.
Klein
J S
JS
Flomenberg
N
N
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000378:metabolism*; D000950:Antigens, Ly / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis / Q000378:metabolism*; D016827:CD8 Antigens; D015536:Down-Regulation; D006801:Humans; D007739:L Cells / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D010766:Phosphorylation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D015704:CD4 Antigens; D016827:CD8 Antigens; D013755:Tetradecanoylphorbol Acetate