Is there a role for Tregs in SIV infected non-human primates? (46.15)

Abstract A study was performed to identify, characterize and compare the level and function of peripheral Tregs in uninfected and SIV-infected rhesus macaques (RM) and sooty mangabeys (SM) to determine if Tregs contribute to the muted immune response that is evident in SIV-infected disease-resistant SM but readily detectable in SIV-infected disease-susceptible RM. Results show that SIV-infected SM maintain the level and function of Tregs but a substantial decline was noted in RM. A strong correlation between plasma VL and the level of Tregs was observed in SIV-infected RM but not SM. RM VL controllers exhibited lower levels of immune activation and recovered pre-infection levels of Tregs that were fully functional when tested for suppressive activity in vitro. ICC assays showed that Treg-depleted PBMC fractions from RM but not SM exhibit increased CD4+ and CD8+ T-cell responses to select SIV peptide pools suggesting that Tregs play a role in the SIV-specific immune response at least in RM. The decline in Tregs in SIV-infected RM as a general consequence of viral pathogenesis may further contribute to the increased immune activation and viral replication exhibited by disease progressors. Although the role of Tregs in SM remains unclear, the data imply that therapeutic manipulationof the frequency and function of Treg-cell in RM and perhaps HIV-infected hosts could improve immune controlof viral infection. NIH RO1 27057, AIDS & Health Sciences Research Grants, Ministry of Health Labor & Welfare in Japan.