HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 NEF DOES NOT ALTER T-CELL SENSITIVITY TO ANTIGEN-SPECIFIC STIMULATION

We have developed an in vitro model to study the influence that human immunodeficiency virus type 1 (HIV-1) may have on the ability of T cel ls to respond to antigenic challenge, We have examined consequences of HIV-1 gene expression on T-cell activation in antigen-dependent T cel ls that have stably integrated copies of replication-defective provira l HIV-1. Virus production by HN-infected, antigen-dependent T cells wa s induced in response to antigenic stimulation and then decreased as i nfected cells returned to a state of quiescence, Contrary to the predi ctions of models proposing that Nef alters signal transduction pathway s in T lymphocytes and thereby alters cellular activation, Nef express ion in antigen-dependent T-cell clones did not influence their prolife rative responses to low or intermediate concentrations of antigen and did not affect other measures of T-cell activation, such as induction of interleukin 2 receptor alpha-chain expression and cytokine producti on, In addition, we found no evidence for alteration of T-cell respons iveness to antigen by the gag, pol, vif, laf, or rev gene of HIV-1.