CD4+ lymphocytes from HIV-infected patients display impaired CD45-associated tyrosine phosphatase activity which is enhanced by anti-oxidants.
It has been proposed that signal transduction defects may, at least partially, account for the functional impairment of CD4+ lymphocytes during HIV-1 infection. Recently, we have demonstrated that unresponsive CD4+ lymphocytes from these patients had reduced protein tyrosine phosphorylation after CD3 engagement, and that this defect was associated with constitutively altered levels of p56lck and p59fyn kinases. Since CD45 is essential for T cell receptor (TCR) and CD2-mediated activation of protein tyrosine kinases, we study here CD45-associated tyrosine phosphatase activity in resting and activated CD4 T cells from HIV-infected patients. We found a significant decrease in the basal and post-activation phosphatase activity of CD45 which correlated well with impairment of proliferative responses. In addition, decreased levels of cellular thiols observed in resting CD4+ lymphocytes from these patients suggested a disturbed redox status. Although expression levels of CD45 were decreased in most patients, a significant recovery of phosphatase activity and proliferative responses was observed in most patients by preincubating cells with N-acetyl-L-cysteine and beta2-mercaptoethanol. In some patients, anti-oxidant treatment failed to significantly enhance phosphatase activity and proliferative responses. The low responses of purified CD4+ lymphocytes from these patients were associated with a high ratio of apoptotic cell death which did not appear to be influenced by anti-oxidant treatment.
Cayota
A
A
Unité d'Immunohématologie et d'Immunopathologie, Institut Pasteur, Paris, France.
Vuillier
F
F
Gonzalez
G
G
Dighiero
G
G
D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology*; D002462:Cell Membrane / Q000201:enzymology; D005434:Flow Cytometry; D015658:HIV Infections / Q000201:enzymology*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008213:Lymphocyte Activation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*
D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases