Characterization of T cells associated with HIV non-progression

Some HIV-infected individuals effectively control HIV infection; these individuals are referred to as long-term non-progressors (LTNPs).  The T cell response may play a major role in controlling viral replication in these individuals.   Therefore, examination of these T cell responses may provide the opportunity to characterize effective immune responses.  Although T cell responses in these LTNPs have been examined previously, the multi-cytokine functional characterization has not been determined.   We propose here to use new flow cytometry-based techniques to examine the expression of 5 or more cytokines simultaneously as well as the expression of memory-defining markers on HIV-specific T cells in LTNPs and in individuals with progressive disease.  This analysis finely dissects the immune response and identifies functional subsets of cells not previously known.  The first aim is to expand the current assays to examine more cytokines and to include multiple T cell differentiation markers.  These expanded assays will be used to characterize the T cell cytokine repertoire, as determined by polyclonal stimulation with SEB in healthy adults.  The second aim is to characterize HIV-specific responses in LTNPs, in progressors, and longitudinally in those LTNPs who subsequently progress.  Statistical analysis will identify the cytokine-defined subsets that are associated with LTNP.  Aim 3 examines epitope-specific responses and compares different epitopes in the same individual and the same epitopes in different individuals.  This will determine whether person-to-person differences or differences in epitopes are the major determinants of differences in cytokine profiles.  The studies proposed here bring a new approach to identifying the features of the immune response unique to LTNPs and thus may identify those features that correlate with efficacy.  Although these investigations are broad in terms of the number of parameters examined, they can potentially identify those key parameters that can serve as the focus of future research in the laboratory and in the clinic.