title: Inhibition of adaptive Vgamma2Vdelta2+ T-cell responses during active mycobacterial coinfection of simian immunodeficiency virus SIVmac-infected monkeys.
abstract: Adaptive immune responses of gammadelta T cells during active mycobacterial coinfection of human immunodeficiency virus-infected humans have not been studied. Macaques infected with the simian immunodeficiency virus (SIV) SIVmac were employed to determine the extent to which a coincident AIDS virus infection might compromise immune responses of mycobacterium-specific Vgamma2Vdelta2(+) T cells during active mycobacterial infection. Control SIVmac-negative macaques developed primary and recall expansions of phosphoantigen-specific Vgamma2Vdelta2(+) T cells after Mycobacterium bovis BCG infection and BCG reinfection, respectively. In contrast, SIVmac-infected macaques did not exhibit sound primary and recall expansions of Vgamma2Vdelta2(+) T cells in the blood and pulmonary alveoli following BCG infection and reinfection. The absence of adaptive Vgamma2Vdelta2(+) T-cell responses was associated with profound CD4(+) T-cell deficiency and subsequent development of SIVmac-related tuberculosis-like disease in the coinfected monkeys. Consistently, Vgamma2Vdelta2(+) T cells from coinfected monkeys displayed a reduced capacity to expand in vitro following stimulation with phosphoantigen. The reduced ability of Vgamma2Vdelta2(+) peripheral blood lymphocytes (PBL) to expand could be restored to some extent by coculture of these cells with CD4(+) T cells purified from PBL of SIV-negative monkeys. Furthermore, naïve monkeys inoculated simultaneously with SIVmac and BCG were unable to sustain expansion of Vgamma2Vdelta2(+) T cells at the time that the coinfected monkeys developed lymphoid depletion and a fatal tuberculosis-like disease. Nevertheless, no deletion in Vdelta2 T-cell receptor repertoire was identified in SIVmac-BCG-coinfected macaques, implicating an SIVmac-induced down-regulation rather than a clonal exhaustion of these cells. Thus, an SIVmac-induced compromise of the adaptive Vgamma2Vdelta2(+) T-cell responses may contribute to the immunopathogenesis of the SIV-related tuberculosis-like disease in macaques.
authors.affiliation: Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Dejiang
authors.initials: D
authors.lastname: Zhou
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Lai
authors.forename: Yun
authors.initials: Y
authors.lastname: Shen
authors.forename: Prabhat
authors.initials: P
authors.lastname: Sehgal
authors.forename: Ling
authors.initials: L
authors.lastname: Shen
authors.forename: Meredith
authors.initials: M
authors.lastname: Simon
authors.forename: Liyou
authors.initials: L
authors.lastname: Qiu
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.forename: George Z
authors.initials: GZ
authors.lastname: Du
authors.forename: Qifan
authors.initials: Q
authors.lastname: Wang
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
authors.forename: Zheng W
authors.initials: ZW
authors.lastname: Chen
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000276:immunology / Q000382:microbiology; D000818:Animals; D006801:Humans; D008213:Lymphocyte Activation; D008251:Macaca; D009163:Mycobacterium bovis / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000276:immunology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D014376:Tuberculosis / Q000150:complications* / Q000276:immunology / Q000382:microbiology
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta