AEGiS-05CROI: Anergy and dysfunction of CD4+ and Vgamma 2Vdelta 2+ lymphocytes associated with Mycobacterium bovis BCG-induced disease in SIV-infected monkeys.

5th Conference on Retroviruses and Opportunistic Infections


Chicago, IL - February 1-5, 1998



Anergy and dysfunction of CD4+ and Vgamma 2Vdelta 2+ lymphocytes associated with Mycobacterium bovis BCG-induced disease in SIV-infected monkeys.

Conf Retroviruses Opportunistic Infect 1998 Feb 1-5; 5th:83 (abstract no. 24)

Zhou Z, Lee-Parritz D, Chalifoux L, Simon M, Morita CT, Letvin NL, Chenz ZW; Beth Israel Deaconess Medical Center, Boston, MA.

Previous studies have demonstrated that macaques coinfected with SIV and Mycobacterium bovis BCG can develop disseminated tuberculosis-like disease and an acceleration in clinical progression of their AIDS. In the present study, the SIV/BCG coinfection model has been employed to explore CD4+ and T cell receptor (TCR) gammadelta + cell responses to mycobacterial peptidic and nonpeptidic antigens in AIDS virus-related tuberculosis. Following BCG infection, normal monkeys exhibited up to a 20-fold expansion of Vgamma2Vdelta2 + cell subpopulation in blood, pulmonary alveoli and intestinal mucosa. This Vgamma2Vdelta2+ cell expansion was associated with a TCR CDR3-dependent expansion of selected Vbeta+ CD4+ cells as well as the emergence of a strong DTH response, to M. bovis PPD and a potent PPD-specific proliferation of CD4+ cells. The expansion of CD4+ and Vgamma2Vdelta2+ cells as well as the emergence of mycobacterial antigen-specific CD4+ cell function correlated with BCG clearance from the blood of the infected monkeys. In contrast, SIV-infected monkeys that were similarly infected with BCG did not show an expansion of Vgamma2Vdelta2+ and Vbeta+ CD4+ cells. In vitro studies demonstrated that PBMC from the SIV-infected but not from uninfected monkeys were nonresponsive to isopentenyl pyrophosphate, a recently-defined nonpeptidic mycobacterial antigen. Interestingly, this decreased expansion of BCG-driven TCR Vbeta-expressing CD4+ and Vgamma2Vdelta2+ cells was associated with energy to PPD skin tests and PPD-driven CD4+ lymphocyte proliferations in the SIV-infected monkeys. Finally, the energy and dysfunction of CD4+ and gammadelta cells coincided with persistently high levels of BCG loads in PBMC of the SIV-infected monkeys. These results provided in vivo evidence implicating TCR Vgamma2Vdelta2+ and selected Vbeta+ CD4+ cells in the anti-mycobacterial immune response, suggesting that AIDS virus-induced energy or dysfunction of CD4+ and gammadelta+ cells may be an underlying mechanism of AIDS virus-related tuberculosis.

Keywords: AEGIS, Mycobacterium bovis, SIV, Antigens, CD4, Simian Acquired Immunodeficiency Syndrome, Tuberculosis, CD4-Positive T-Lymphocytes, Tuberculin, Receptors, Antigen, T-Cell, Acquired Immunodeficiency Syndrome, Macaca, Animal, In Vitro, AIDSKWDaegis,mycobacteriumbovis,siv,antigens,cd4,simianacquiredimmunodeficiencysyndrome,tuberculosis,cd4-positivet-lymphocytes,tuberculin,receptors,antigen,t-cell,acquiredimmunodeficiencysyndrome,macaca,animal,invitro,aids

1998-02-01
24

Copyright © 1998 - Foundation for Retrovirology and Human Health (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed from National Library of Medicine.