ENDOGENOUS PRODUCTION OF BETA-CHEMOKINES BY CD4(-CELL CLONES CORRELATES WITH THE CLINICAL STATE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1)-INFECTED INDIVIDUALS AND MAY BE RESPONSIBLE FOR BLOCKING INFECTIONWITH NON-SYNCYTIUM-INDUCING HIV-1 IN-VITRO(), BUT NOT CD8(+) T)

Recent studies have demonstrated that the beta-chemokines RANTES, MIP- 1 alpha, and MIP-1 beta suppress human immunodeficiency virus type 1 ( HIV-1) replication in vitro and may play an important role in protecti ng exposed but uninfected individuals from HIV-1 infection. However, l evels of beta-chemokines in AIDS patients are comparable to and can ex ceed levels in nonprogressing individuals, indicating that global beta -chemokine production may have little effect on HIV-1 disease progress ion. We sought to clarify the role of beta-chemokines in nonprogressor s and AIDS patients by examination of beta-chemokine production and HI V-1 infection in patient T-lymphocyte clones established by herpesviru s saimiri immortalization. Both CD4(+) and CD8(+) clones were establis hed, and they resembled primary T cells in their phenotypes and expres sion of activated T-cell markers. CD4(+) T-cell clones from all patien ts had normal levels of mRNA-encoding CCR5, a coreceptor for non-syncy tium-inducing (NSI) HIV-1. CD4(+) clones from nonprogressors and CD8() clones from AIDS patients secreted high levels of RANTES, MIP1 alpha , and MIP-1 beta. In contrast, CD4(+) clones from AIDS patients produc ed no RANTES and little or no MIP-1 alpha or MIP-1 beta. The infection of CD4(+) clones with the NSI HIV-1 strain ADA revealed an inverse co rrelation to beta-chemokine production; clones from nonprogressors wer e poorly susceptible to ADA replication, but clones from AIDS patients were highly infectable. The resistance to ADA infection in CD4(+) clo nes from nonprogressors could be partially reversed by treatment with anti-beta-chemokine antibodies. These results indicate that CD4(+) cel ls can be protected against NSI-HIV-1 infection in culture through end ogenously produced factors, including beta-chemokines, and that beta-c hemokine production by CD4(+), but not CD8(+), T cells may constitute one mechanism of disease-free survival for HIV-1-infected individuals.