Perforin-Low Memory Cd8(+) Cells Are The Predominant T Cells In Normal Humans That Synthesize The Beta-Chemokine Macrophage Inflammatory Protein-1 Beta

The synthesis of antiviral beta -chemokines has joined cytolysis as a potential mechanism for the control of HIV-1 infection by CD8(+) T cells. Recent evidence suggests that these two effector functions can diverge in some individuals infected with HIV-1; however, little is known about the CD8(+) T cell subsets in normal individuals that synthesize antiviral beta -chemokines. In this report, we have used mutliparameter flow cytometry to characterize the T cell subsets that secrete the antiviral beta -chemokine macrophage inflammatory protein (MIP)-1 beta. These studies have shown: (i) CD8+ cells are the predominant T cell subset that synthesizes MIP-1 beta; (ii) MIP-1 beta and IFN-gamma are synthesized congruently in most CD8(+) T cells; however, significant numbers of these cells synthesize only one of these effector molecules; (iii approximately 60% of the CD8(+) T cells that synthesize MIP-1 beta lack perforin; (iv) MIP-1 beta is synthesized with approximately equal frequency by CD28(+) and CD28(-) subpopulations of CD8(+) T cells; (iv) MIP-1 beta is synthesized by three distinct CD8(+) T cell subsets defined by the expression of CD45R0 and CD62L; and (vi) MIP-1 beta is not synthesized in short-term cultures of naive CD8(+) T cells. These results demonstrate substantial subset heterogeneity of MIP-1 beta synthesis among CD8(+) T cells and suggest that these subsets should be evaluated as correlates of protective immunity against HIV-1.