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-l-infected patients there was a preferential depletion of CD45RA(+)CD4(+) cells, which was most pronounced in symptomatic patients, In CD4(+) lymphocytes from HIV-l-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 CD45RA(+) 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. (C) 1996 by The American Society of Hematology.