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In vitro antioxidant treatment recovers proliferative responses of anergic
CD4+ lymphocytes from human immunodeficiency virus-infected individuals
A Cayota, F Vuillier, G Gonzalez and G Dighiero
Unite d' Immunohematologie et d'Immunopathologie, Institut Pasteur, Paris
France.
Oxidative stress has been proposed to be involved in the immunologic defeat
observed in effector calls of the immune system as well as in lymphocyte
cell death and viral replication in human immunodeficiency virus
(HIV)-infected patients. Because thiol-containing antioxidants such as
N-acetyl-L-cysteine have been shown to have beneficial effects on CD4+
lymphocyte survival and to inhibit programmed cell death and HIV-1
replication, they may play a role in therapeutic strategies of this
disease. In this work we have studied the cellular thiol levels and the
affect of in vitro antioxidant treatment of purified CD4+ lymphocytes from
HIV-infected patients, and correlated these parameters to proliferative
responses and programmed cell death. We show that CD4+ lymphocytes from
HIV-infected patients display impaired proliferative responses and a
significant decrease in cellular thiol levels, indicating a disturbed redox
status. Interestingly, antioxidant treatment succeeded to restore defective
proliferative responses to CD3- mediated activation in 8 of 11 patients
(high antioxidant responders). In contrast to high responders, patients
failing to respond to antioxidant treatment (low antioxidant responders),
were characterized by an abnormal ratio of apoptotic cells, which was not
affected by N- acetyl-L-cysteine and/or 2-beta-mercaptoethanol
preincubation. These results demonstrate for the first time that
antioxidant treatment is able to revert the impaired proliferative activity
of CD4 cells from HIV-infected patients and could help designing
therapeutic strategies with antioxidant drugs. However, this action is not
observed in cells undergoing programmed cell death.
Volume 87,
Issue 11,
pp. 4746-4753,
06/01/1996
Copyright © 1996 by The American Society of Hematology
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