Suppression of intracellular hydrogen peroxide generation and catalase levels in CD8+ T-lymphocytes from HIV+ individuals.
CD8+ T-lymphocytes from HIV+ individuals contain short telomeres, a sign of cell senescence. To test our hypothesis that the cell type is functionally defective in the biochemical indices related to cell proliferation, we investigated the profiles of intracellularly generated H2O2 levels with or without PMA as well as immunoreactive catalase levels using flow cytometric method. We observed that, in HIV+ but not in HIV- individuals, the constitutively generated H2O2 level was significantly lower in CD8+ T-cells compared with CD4+ T-cells. Importantly, activated effector CD8+CD28- cells showed remarkably low H2O2 levels compared with CD8+CD28+ cells, and the latter in HIV+ individuals also showed low levels. A similar defect of CD8+ cells of HIV+ individuals was also seen with H2O2 levels stimulated with PMA in the presence of a catalase inhibitor. Furthermore, the immunoreactive catalase content was lower in CD8+ cells compared with CD4+ cells only in HIV+ individuals. These results suggest that CD8+ T-lymphocytes are functionally defective with the constitutively generated and PMA-elicited levels of H2O2 and the corresponding scavenger. Diminished immunocompetence of HIV+ individuals may be caused, in part, by the functional defect of CD8+ T-cells.
Yano
S
S
Department of Biochemistry, Ponce School of Medicine, Puerto Rico.
Yano
N
N
Rodriguez
N
N
Baek
J H
JH
Que
X
X
Yamamura
Y
Y
Kim
S J
SJ
D000328:Adult; D000640:Amitrole / Q000494:pharmacology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002374:Catalase / Q000037:antagonists & inhibitors / Q000097:blood*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006679:HIV Seropositivity / Q000097:blood*; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood*; D018655:Lymphocyte Count; D008875:Middle Aged; D011493:Protein Kinase C / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004791:Enzyme Inhibitors; D006861:Hydrogen Peroxide; D002374:Catalase; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D000640:Amitrole