title: 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.
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.
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Shen
authors.forename: Yun
authors.initials: Y
authors.lastname: Shen
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.forename: Liyou
authors.initials: L
authors.lastname: Qiu
authors.forename: Prabhat
authors.initials: P
authors.lastname: Sehgal
authors.forename: George Z
authors.initials: GZ
authors.lastname: Du
authors.forename: Michael D
authors.initials: MD
authors.lastname: Miller
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
authors.forename: Zheng W
authors.initials: ZW
authors.lastname: Chen
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002417:Cattle; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D019469:Indinavir / Q000627:therapeutic use; D008168:Lung / Q000276:immunology; D018655:Lymphocyte Count; D008253:Macaca mulatta; D008254:Macaca nemestrina; D008969:Molecular Sequence Data; D009163:Mycobacterium bovis / Q000276:immunology; D063065:Organophosphonates / Q000627:therapeutic use; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis* / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000302:isolation & purification; D000068698:Tenofovir; D014380:Tuberculosis, Bovine / Q000150:complications / Q000276:immunology*
chemical_list: D017320:HIV Protease Inhibitors; D063065:Organophosphonates; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018894:Reverse Transcriptase Inhibitors; D019469:Indinavir; D000068698:Tenofovir; D000225:Adenine