We investigated mechanisms by which the soluble native envelope glycoprotein gp120 of the human immunodeficiency virus (HIV-1) suppresses antigen-driven T cell responses. For this study, exogenous interleukin-2 (IL-2)-independent, antigen-specific, CD4 positive, human T-cell clones were developed by cyclic restimulation with soluble tetanus toxoid antigen. In the presence of soluble antigen and antigen- presenting cells (APC), T-cell clones proliferated and secreted IL-2. Purified gp120 suppressed the proliferative responses of the T-cell clones with concomitant suppression of IL-2 secretion; proliferative responses of CD8+ T cells preincubated with gp120 were not inhibited. A short pulse of 20 minutes with gp120 was sufficient to inhibit the proliferative response of the T-cell clones. Anti-CD3 monoclonal antibody (MoAb)-driven proliferation of the T-cell clones was also suppressed by gp120, but responses elicited by mitogens, phorbol myristate acetate (PMA) plus calcium ionophore, ionomycin, anti-CD2 MoAbs, and a combination of anti-CD3 plus anti-CD28 MoAb driven responses remained unaffected. Investigation of signal transduction events showed that antigen-driven early activation signals via translocation of protein kinase C (PKC), increase in intracellular inositol phosphates, and increase in intracellular calcium were suppressed in gp120 pretreated, tetanus toxoid antigen-stimulated T- cell clones. One mechanism of immune suppression by gp120 may involve interference with the initiation of signal transduction through the T- cell receptor complex.
Inhibition of functional properties of tetanus antigen-specific T-cell clones by envelope glycoprotein GP120 of human immunodeficiency virus
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N Chirmule, VS Kalyanaraman, N Oyaizu, HB Slade, S Pahwa; Inhibition of functional properties of tetanus antigen-specific T-cell clones by envelope glycoprotein GP120 of human immunodeficiency virus. Blood 1990; 75 (1): 152–159. doi: https://doi.org/10.1182/blood.V75.1.152.bloodjournal751152
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