High IL-10 production by aged AIDS patients is related to high frequency of Tr-1 phenotype and low in vitro viral replication

This work aims to elucidate the effects of age and HIV-1 infection on the frequency and function of T cell subsets in response to HIV-specific and non-specific stimuli. As compared with the younger AIDS group, the frequencies of naive and central memory T cells were significantly lower in aged AIDS patients. Although there was also a dramatic loss of classical CD4+FoxP3+CD25+Treg cells in this patient group, high frequencies of IL-10-producing CD4+FoxP3− T cells were observed. In our system, the increased production of IL-10 in aged AIDS patients was mainly derived from Env-specific CD4+FoxP3−CD152+ T cells. Interestingly, while the blockade of IL-10 activity by monoclonal antibody clearly enhanced the release of IL-6 and IL-1β by Env-stimulated PBMC cultures from aged AIDS patients, this monoclonal antibody enhanced in vitro HIV-1-replication. In conclusion, HIV infection and aging undoubtedly contribute synergistically to a complex immune dysfunction in T cell compartment of HAART-treated older HIV-infected individuals.

► Aging reduces the frequency of HIV-1-specific IFN-γ-producing T cells.
► A dramatic loss of CD4+CD25+FoxP3+ Treg cells was observed in aged AIDS patients.
► Aging enhances the frequency of HIV-1-specific IL-10-producing CD4+FoxP-CD152+T-cells.
► IL-10 elevated HIV-1 replication by reducing IL-6 and IL-1β release.