Inhibition of protein kinase C-mediated CD4 down-regulation by oxidative stress in T lymphocytes.
The CD4 molecule acts as a receptor for class II MHC molecules to stabilize Ag recognition by the TCR and as a high affinity receptor for HIV-1. In this study, we investigated the effect of oxidative stress on the level of CD4 expression on cultured peripheral blood T lymphocytes (PBL blasts). As previously reported, we observed that the surface CD4 was down-regulated by PMA. Unexpectedly, treatment of PBL blasts with hydrogen peroxide (H2O2) or a sulfhydryl oxidative reagent, diamide, almost completely inhibited PMA-induced CD4 down-regulation, although these oxidants per se did not affect the level of CD4 expression. We next assessed the serine phosphorylation of CD4, which is reported to be an indispensable process for PMA-induced CD4 endocytosis. PMA could induce the serine phosphorylation even in the presence of oxidants. We also found that these oxidants had an additive effect on PMA-induced dissociation between CD4 and p56(lck), which is known to be another necessary step for CD4 endocytosis. These results indicate that in T cells, oxidants inhibit protein kinase C-mediated CD4 down-regulation due to perturbing a signaling process other than the above two steps, implying that oxidative stress may tune the functions of CD4+ T cells and their susceptibility to HIV-1 through the control of CD4 expression.
Nakamura
K
K
Department of Biological Responses, Institute for Virus Research, Kyoto University, Japan.
Sasada
T
T
Sono
H
H
Yodoi
J
J
D015704:CD4 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011493:Protein Kinase C / Q000502:physiology*; D013312:Stress, Physiological / Q000503:physiopathology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019061:src-Family Kinases / Q000378:metabolism
D015704:CD4 Antigens; D016877:Oxidants; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate