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Journal of Virology, March 2003, p. 2998-3006, Vol. 77, No. 5
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.5.2998-3006.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Inhibition of Adaptive V{gamma}2V{delta}2+ T-Cell Responses during Active Mycobacterial Coinfection of Simian Immunodeficiency Virus SIVmac-Infected Monkeys

Dejiang Zhou,1,2 Xiaomin Lai,1,2 Yun Shen,1,2 Prabhat Sehgal,3 Ling Shen,2 Meredith Simon,3 Liyou Qiu,1,2 Dan Huang,1,2 George Z. Du,1,2 Qifan Wang,1,2 Norman L. Letvin,2 and Zheng W. Chen1,2*

Tuberculosis Research Unit,1 Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215,2 Harvard Medical School, New England Regional Primate Research Center, Southboro, Massachusetts 017723

Received 18 September 2002/ Accepted 5 December 2002

Adaptive immune responses of {gamma}{delta} 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 V{gamma}2V{delta}2+ T cells during active mycobacterial infection. Control SIVmac-negative macaques developed primary and recall expansions of phosphoantigen-specific V{gamma}2V{delta}2+ 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 V{gamma}2V{delta}2+ T cells in the blood and pulmonary alveoli following BCG infection and reinfection. The absence of adaptive V{gamma}2V{delta}2+ 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, V{gamma}2V{delta}2+ T cells from coinfected monkeys displayed a reduced capacity to expand in vitro following stimulation with phosphoantigen. The reduced ability of V{gamma}2V{delta}2+ 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 V{gamma}2V{delta}2+ T cells at the time that the coinfected monkeys developed lymphoid depletion and a fatal tuberculosis-like disease. Nevertheless, no deletion in V{delta}2 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 V{gamma}2V{delta}2+ T-cell responses may contribute to the immunopathogenesis of the SIV-related tuberculosis-like disease in macaques.

* Corresponding author. Mailing address: Beth Israel Deaconess Medical Center, 330 Brookline Ave., RE113, Boston, MA 02215. Phone: (617) 667-2061. Fax: (617) 667-8210. E-mail: zchen{at}caregroup.harvard.edu.

Journal of Virology, March 2003, p. 2998-3006, Vol. 77, No. 5
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.5.2998-3006.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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