Recent studies have demonstrated that the
beta-chemokines RANTES,
MIP-1alpha, and
MIP-1beta 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, MIP1alpha, and
MIP-1beta. In contrast, CD4+ clones from
AIDS patients produced no
RANTES and little or no
MIP-1alpha or
MIP-1beta. 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.