Role of the CD4 Receptor in Human T Lymphocyte Signalling: Effects of HIV-1 Infection on Human T Cell Activation

It has previously been shown that infection of human CD4 cells with human immunodeficiency virus HIV-1 results in the establishment of a chronic, non-cytopathic infection. We have recently found that cells infected with HIV-1 exhibit a specific impairment of cellular signalling. After polyclonal stimulation of the CD3T cell receptor complex by anti-CD3 monoclonal antibody, the cells have a blunted or absent increase in the intracellular free calcium concentration within the first three minutes after simulation. In the present study we have investigated the mechanisms of the effect on cellular signalling by HIV-1. CD4 T cells were infected with HIV-1 and labeled with myoinositol. Inositol phosphate production was impaired after CD3 stimulation, suggesting that the effect of HIV-occurs at or before the activation of phosphoinositide specific phospholipase C. Recent studies have shown that the CD4 molecule is involved in cellular signalling with the T cell receptor as well as functioning as a receptor for MHC class II antigen and as the receptor for the HIV-1 virus. To further investigate the effects of HIV-1 on cellular signalling, the CEM leukemic T cell line was chronically infected with HIV-1, or a spontaneous mutant strain of HIV-1 that fails to cause modulation of the CD4 antigen. Calcium mobilization was impaired in cells infected with both strains of virus, indicating that impaired signalling is not simply the result of decreased surface expression of the CD4 receptor. Reprints. kt