Decreased HIV-Specific T-Regulatory Responses Are Associated with Effective DC-Vaccine Induced Immunity

The role of regulatory t cells (tregs) in vaccination has been poorly investigated. we have reported that vaccination with ex vivo-generated dendritic-cells (dc) loaded with hiv-lipopeptides (lipo-5-dc vaccine) in hiv-infected patients was well tolerated and highly immunogenic. these responses and their relation to viral replication following analytical treatment interruption (ati) were variable. here,we investigated whether the presence of hiv-specific tregs might explain these differences. co-expression of cd25,cd134,cd39 and foxp3 was used to delineate both antigen-specific tregs and effectors t cells (teffs). median lipo-5 specific-cd25+cd134+ polyfunctional t cells increased from 0.1% (iqr 0-0.3) before vaccination (week -4) to 2.1% (iqr 1.1-3.9) at week 16 following 4 immunizations (p=0.001) and were inversely correlated with maximum viral load following ati (r=-0.77,p=0.001). vaccinees who displayed lower levels of hiv-specific cd4+cd134+cd25+cd39+foxp3+ tregs responded better to the lipo-5-dc vaccine. after vaccination,the frequency of hiv-specific tregs decreased (from 69.3 at week -4 to 31.7% at week 16) and inversely correlated with hiv-specific ifn-γ-producing cells (r=-0.64,p=0.002). we show that therapeutic immunization skewed the hiv-specific response from regulatory to effector phenotype which impacts on the magnitude of viral replication following ati. © 2015 brezar et al.