Endogenous production of beta-chemokines by CD4(+), but not CD8(+) T-cell clones correlates with the clinical state of human immunodeficiency virus type 1 (HIV-1)-infected individuals and may be responsible for blocking infection with non-syncytium-inducing HIV-1 in vitro

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 protecting exposed but uninfected individuals from HIV-1 infection. However, levels of beta-chemokines in AIDS patients are comparable to and can exceed levels in nonprogressing individuals, indicating that global beta-chemokine production may have little effect on HIV-1 disease progression. We sought to clarify the role of beta-chemokines in nonprogressors and AIDS patients by examination of beta-chemokine production and HIV-1 infection in patient T-lymphocyte clones established by herpesvirus saimiri immortalization. Both CD4(+) and CD8(+) clones were established, and they resembled primary T cells in their phenotypes and expression of activated T-cell markers. CD4(+) T-cell clones from all patients had normal levels of mRNA-encoding CCR5, a coreceptor for non-syncytium-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 produced 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 correlation to beta-chemokine production; clones from nonprogressors were poorly susceptible to ADA replication, but clones from AIDS patients were highly infectable. The resistance to ADA infection in CD4(+) clones from nonprogressors could be partially reversed by treatment with anti-beta-chemokine antibodies. These results indicate that CD4(+) cells can be protected against NSI-HIV-1 infection in culture through endogenously produced factors, including beta-chemokines, and that beta-chemokine production by CD4(+), but not CD8(+), T cells may constitute one mechanism of disease-free survival for HIV-1-infected individuals.