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HIV infection--induced posttranslational modification of T cell signaling molecules associated with disease progression.

1996; American Society for Clinical Investigation; Volume: 98; Issue: 6 Linguagem: Inglês

10.1172/jci118915

1558-8238

Irena Štefanová, M. Wayne Saville, Christian Peters, Farley Cleghorn, Daniella M. Schwartz, David Venzon, Kent J. Weinhold, Noreen Jack, C Bartholomew, W. A. Blattner, Robert Yarchoan, Joseph B. Bolen, Ivan D. Horak,

T-cell and Retrovirus Studies

In attempt to elucidate the mechanism of the HIV infection induced T cell unresponsiveness, we studied signal-transducing molecules proximal to the T cell receptor (TCR) in T lymphocytes of HIV-infected individuals. Total amounts of protein tyrosine kinases (PTKs) Lck, Fyn, and ZAP-70 and the zeta chain of the TCR were found significantly decreased in T cells of symptomatic/AIDS patients as well as in T cells of individuals in acute and early asymptomatic stages of HIV infection. Unexpectedly, the detection of Lck, Fyn, and ZAP-70 was reversed after the treatment of cell lysates with dithiothreitol. This suggests that PTKs Lck, Fyn, and ZAP-70 were modified by a mechanism altering the status of sulfhydryl groups. Moreover, this mechanism seems to affect selectively T cells of HIV infected patients since B cell PTKs Syk and Lyn were detected structurally and functionally intact. Interestingly, similar alterations of signaling molecules were not detected in T cells of HIV-infected long-term asymptomatic individuals. Modification of T cell PTKs may thus underlie the HIV-induced impairment of lymphocyte function and may potentially predict disease progression.