An early and robust natural killer cell response during acute SIV infection in sooty mangabeys but not rhesus macaques is correlated with disease resistance

Abstract

A need for defining optimal reagents and assays to identify the NK cell lineage in non‐human primates (NHP) is required because recent data clearly implicate an important role for NK cells in contributing to disease progression in HIV‐1 infected individuals. This cell lineage is particularly involved in the acute phase of infection which can optimally be studied in SIV infected NHP. A study of the role of NK cells in SIV infected disease resistant sooty mangabeys (SM) as compared with SIV infected disease susceptible rhesus macaques (RM) may provide important clues as to the contributing role of NK cells in the polarized clinical outcome in these two species. The use of previously identified reagents along with newly defined reagents and multi‐color flow cytometry has revealed that a gated population of CD3− CD8+ NKG2A+ cells identify 4 NK cell subsets with a predominant CD16+ CD56− subset primarily contributing to functional NK cytolytic activity. Cross sectional studies revealed a significant decline in this cytolytic subset in SIV‐infected RM but not in SIV‐infected SM. Importantly, longitudinal studies of individual animals pre and post SIV infection showed that while infection induces transient increases in NK cells in both species, there was a marked difference in the kinetics by which such increases occurred with SIV‐infected SM exhibiting a much earlier and more robust NK response than SIV‐infected RM.