Journal of Antivirals & Antiretrovirals
Open Access

In vitro restoration of Th17 response during HIV infection with an antiretroviral drug and Th17 differentiation cytokines

International Conference and Exhibition on VIROLOGY

5-7 September 2011 Baltimore, USA

Catarina E. Hioe

Scientific Tracks Abstracts: JAA

Abstract :

HIV infection is marked by a profound loss of CD4 T cells and functions. Th e Th 17 subset, which plays an important role in the control of extracellular bacteria and fungi, is particularly depleted as compared to the Th 1 subset in chronically HIV-infected patients, even aft er sustained virus-suppressive anti-retroviral therapy. In this study, we have established an in vitro system utilizing primary human CD4 T cultures that recapitulates the dramatic loss of Th 17 response upon HIV-1 infection with a less profound decrease of Th 1 response. With this experimental system, we showed that active HIV-1 replication was needed for the depletion of Th 17 response. Blocking viral entry with CCR5 ligands or TAK779 reduced the infection and enhanced Th 17 response but not Th 1 response. Th e more potent anti-retroviral drug 3TC, given at the time of infection, prevented the loss of both Th 17 and Th 1 responses, but was not eff ective when given aft er infection was already established. Only when Th 17 diff erentiation cytokines were given along with 3TC to the infected cultures, was Th 17 cell response fully restored. Finally, up to 3 fold increase of Th 17 response was achieved in PBMCs of patients on antiretroviral therapy aft er treatment with Th 17 diff erentiation cytokines. Th ese data demonstrate the presence of CD4 T cells remaining capable of mounting Th 17 response during HIV infection and indicate the potential use of immunotherapeutic modalities to supplement anti-retroviral drugs for restoring Th 17 response in chronically HIV infected patients.