Markedly disturbed glutathione redox status in CD45RA+CD4+ lymphocytes in human immunodeficiency virus type 1 infection is associated with selective depletion of this lymphocyte subset.
We investigated the percentage of CD45RA+ and CD45RO+ T cells in peripheral blood and the intracellular glutathione redox balance in these lymphocyte subsets in patients with human immunodeficiency virus type 1 (HIV-1) infection and healthy controls. In HIV-1-infected patients there was a preferential depletion of CD45RA+CD4+ cells, which was most pronounced in symptomatic patients. In CD4+ lymphocytes from HIV-1-infected patients the glutathione abnormalities were clearly most pronounced in the CD45RA+ subset with a marked increase in level of oxidized glutathione and decreased ratio of reduced to total glutathione as the major characteristics. These abnormalities were shown in CD45RA+ CD4+ lymphocytes from both symptomatic and asymptomatic patients, whereas similar abnormalities in CD45RO+CD4+ cells were found only in symptomatic patients. The glutathione abnormalities in CD45RA+CD4+ lymphocytes were significantly correlated with low numbers of total CD4+ lymphocytes, decreased proportion of CD45RA+CD4+ lymphocytes, and raised serum levels of tumor necrosis factor-alpha. In the CD8+ lymphocytes a decrease in both proportion and absolute numbers of CD45RA+ cells was found, with markedly increased level of oxidized glutathione and decreased ratio of reduced to total glutathione in this subset. These findings suggest that glutathione redox disturbances in CD45RA+ T cells may be of pathogenic importance for the preferential depletion of this subset considered to represent naive T cells, during HIV-1 infection.
Aukrust
P
P
Medical Department A, University of Oslo, National Hospital, Norway.
Svardal
A M
AM
Müller
F
F
Lunden
B
B
Nordøy
I
I
Frøland
S S
SS
D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000097:blood*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis*; D016131:Lymphocyte Subsets / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D014409:Tumor Necrosis Factor-alpha; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D005978:Glutathione