Acquisition of HIV type 1 resistance by beta-chemokine-producing CD4(+) T cells

The CD4(+) T cell is a major target cell type for human immunodeficiency vi rus type 1 (HIV-1) infection. In this study, we provide evidence that the s usceptibility to HIV-1 infection is variable in individual CD4(+) T cells. Five CD4(+) T cell clones were isolated from an HIV-1-seronegative donor an d were investigated for their susceptibility to HIV-1 infection. Four CD4() T cell clones were resistant to infection by a macrophage-tropic (R5) HIV -1 isolate whereas one clone was fully permissive. The level of susceptibil ity to HIV-1 correlated inversely with beta-chemokine production, including RANTES (regulated on activation, normally T cell expressed and secreted), macrophage inflammatory protein 1 alpha (MIP-1 alpha), and MIP-1 beta, Resi stance to HIV-1 infection was abrogated by the combined use of neutralizing antibodies against these three beta-chemokines. Interestingly, a complete inhibition of HIV-1 infection was observed in peripheral blood mononuclear cells on infection induced by adding the culture supernatant or a small num ber of HIV-1-resistant cell clones. Our results suggest the presence of a c lonal self-defense mechanism within the CD4+ T cell population in vivo that involves the secretion of beta-chemokines.