Development of Vgamma2Vdelta2+ T cell responses during active mycobacterial coinfection of simian immunodeficiency virus-infected macaques requires control of viral infection and immune competence of CD4+ T cells

J Infect Dis. 2004 Oct 15;190(8):1438-47. doi: 10.1086/423939. Epub 2004 Sep 10.

Abstract

Vgamma2Vdelta2+ T cells play a role in antimicrobial responses. It is unknown whether adaptive Vgamma2Vdelta2+ T cell responses during active mycobacterial coinfection of human immunodeficiency virus-infected humans can be generated during effective antiretroviral treatment. Here, simian immunodeficiency virus (SIV)mac-infected macaques previously exposed to bacille Calmette-Guerin (BCG) were reinfected with BCG, were treated either with tenofovir or tenofovir plus indinavir, and were assessed for the development of Vgamma2Vdelta2+ T cell responses during active BCG coinfection. A restored capacity of Vgamma2Vdelta2+ T cells to undergo major expansions and pulmonary migration during active BCG coinfection was detected after simultaneous BCG reinfection and treatment with tenofovir of the SIVmac-infected macaques. Interestingly, a restored expansion of Vgamma2Vdelta2+ T cells in the SIVmac/BCG-coinfected macaques was detectable, even though antiretroviral treatment was initiated 1 month after BCG reinfection. Importantly, the restored expansion of Vgamma2Vdelta2+ T cells coincided with increases in numbers of purified protein derivative-specific interferon- gamma -producing CD4+ T cells and increases in the magnitude of their proliferative responses. In contrast, the SIVmac-infected control macaques exhibited diminished responses of Vgamma2Vdelta2+ T cells and mycobacterium-specific CD4+ T cells during active BCG coinfection. Our results suggest that the development of adaptive immune responses of phosphoantigen-specific Vgamma2Vdelta2+ T cells during active mycobacterium/HIV coinfection requires control of viral infection and immune competence of peptide-specific CD4+ T cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Amino Acid Sequence
  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Cattle
  • Disease Models, Animal
  • Drug Therapy, Combination
  • HIV Protease Inhibitors / therapeutic use
  • Indinavir / therapeutic use
  • Lung / immunology
  • Lymphocyte Count
  • Macaca mulatta
  • Macaca nemestrina
  • Molecular Sequence Data
  • Mycobacterium bovis* / immunology
  • Organophosphonates / therapeutic use
  • Receptors, Antigen, T-Cell, gamma-delta / analysis*
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Simian Acquired Immunodeficiency Syndrome / complications
  • Simian Acquired Immunodeficiency Syndrome / drug therapy
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Immunodeficiency Virus* / isolation & purification
  • Tenofovir
  • Tuberculosis, Bovine / complications
  • Tuberculosis, Bovine / immunology*

Substances

  • HIV Protease Inhibitors
  • Organophosphonates
  • Receptors, Antigen, T-Cell, gamma-delta
  • Reverse Transcriptase Inhibitors
  • Indinavir
  • Tenofovir
  • Adenine