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. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The purpose of the study was to evaluate the effect of continuous ART on innate and adaptive peripheral and mucosal immune responses and determine whether PolyIC can boost oral immunity in ART-treated animals. 2000 TCID^50 of wild type SIVmac239 was applied to the tonsils of 12 animals, 10 of which became infected. These 10 infected animals and the 8 uninfected animals were divided into the ART vs no ART groups. Despite the initial peak plasma viremias decreasing more rapidly in all animals of the ART-receiving group, 2 animals did not control virus under ART. PolyICLC treatment of the tonsils was being used as a tool to evaluate oral immune function under ART. During the acute phase of infection (week 2), increased frequency of PDCs, increased frequency of effector memory CD4+T cells and decreased percentages of CD4+ central memory T cells were observed in the blood. Chronically (at week 28) we found no significant differences between the groups. Immediately, after polyICLC application, we detected an up-regulation of CD80 on MDC in all groups (after the second and fourth treatments). There also appeared to be an increase of Foxp3+Treg over time in all groups following the polyICLC applications. SIV and Candida albicans-specific CD4+ and CD8+ T cell responses were detected by 4-color (TNF/IL-2/IFN gamma/IL-17) intracellular cytokine staining at weeks 26, 34, 51 and at the time point of necropsy. TNFgamma and IFN gamma-producing SIV-specific CD4+ and CD8+ T cell responses were stronger in SIV+ART- group compared to SIV+ART+ but did not reach statistical significance. There also appeared to be a decrease of Candida-specific CD4+ T cell responses after PolyICLC application (all cytokines). Increased levels of CXCL10 were detected in oral swabs in 9 out of 18 animals after the first PolyICLC application.