IMPACT OF ART ON DC & TREG RESPONSES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We hypothesized that ART initiated during the early stages of pathogenic SIV infection (prior to significant immune damage) will have little, if any, impact on oral immune function. This will contrast untreated SIV infection in which oral (and systemic) immune functions are ultimately destroyed. Specifically, we propose that untreated SIV infection will impede innate DC (and EC) functions to favor the expansion of Tregs and further dampen effector responses needed to control oral pathogens. We believe that basic oral immune function in infected animals receiving ART will be comparable to that seen in uninfected animals (with or without ART). To evaluate the effect of continuous ART on innate and adaptive oral mucosal immune responses. 18 Indian male rhesus monkeys were included in the study. 12 animals were challenged with 2000 TCID50 of wtSIVmac239 on the tonsils. ART was commenced 2 weeks after SIV challenge allowing initial virus expansion. Uninfected animals received ART in parallel. ART regimen involved combined treatment with PMPA (20 mg/kg/d s.c.) and FTC (40 mg/kg/d s.c.). This was given for 34 weeks in total. The SIV infected and ART treated animals maintained normal oral and systemic immune functions with lower viral set point. Whereas, significant destruction of the immune system, disease progression, and much higher viral set points were observed the SIV infected ART untreated animals.