Pilot Award

Natural occurring CD4+CD25+ regulatory T (T-reg) cells have broad immunotherapeutic applications and a greater understanding of the factors influencing their function is important. During untreated early HIV-1 infection there is a progressive and preferential expansion of circulating T-reg cells and such accumulation plays an important role in the inability of the immune system to control viral replication. Despite renewed focus on suppressive T-reg cells, the existence of a reciprocal pathway of immune "contrasuppression" has been suggested by clonal studies in mice. We have recently demonstrated the existence of novel CD4+ T "inducer" (T-ind) cell subset expressing the CD39/(NTPDase1) ectoenzyme in peripheral blood of uninfected subjects that potently enhances T cell immune responses in vitro. We propose to repeat that method of discovery now focused on the full characterization and examination of the consequences of these immunoregulatory CD4+ T cell subsets in both cross-sectional and longitudinal studies of early HIV-1 infected subjects. The development of effective approaches for the clinical manipulation of regulatory T cells (T-reg and T-ind) cells will be dependent on the clear understanding of how these sophisticated regulatory mechanisms maintain immune homeostasis.