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

Clin Immunol. 2012 Oct;145(1):31-43. doi: 10.1016/j.clim.2012.08.002. Epub 2012 Aug 17.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / drug therapy
  • Acquired Immunodeficiency Syndrome / immunology*
  • Acquired Immunodeficiency Syndrome / virology
  • Adult
  • Age Factors
  • Antibodies, Monoclonal / pharmacology
  • Antiretroviral Therapy, Highly Active
  • Antiviral Agents / administration & dosage
  • Cells, Cultured
  • Female
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Immunologic Memory
  • Immunophenotyping
  • Interleukin-10 / antagonists & inhibitors
  • Interleukin-10 / immunology*
  • Interleukin-1beta / biosynthesis
  • Interleukin-1beta / immunology
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / immunology
  • Male
  • Middle Aged
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / pathology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / pathology
  • Virus Replication / drug effects

Substances

  • Antibodies, Monoclonal
  • Antiviral Agents
  • IL10 protein, human
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-10