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Mycobacterium tuberculosis Recall Antigens Suppress HIV-1 Replication in Anergic Donor Cells via CD8⁺ T Cell Expansion and Increased IL-10 Levels¹

Shahin Ranjbar^*, Nary Ly, Sok Thim, Jean-Marc Reynes and Anne E. Goldfeld^2,*

^* Center for Blood Research and Department of Medicine, Harvard Medical School, Boston, MA 02115; Unité de Virologie, Institut Pasteur du Cambodge, Phnom Penh, Cambodia; and Cambodian Health Committee, Phnom Penh, Cambodia

Mycobacterium tuberculosis (MTb) is the leading cause of death in the setting of AIDS. MTb enhances the pathogenicity and accelerates the course of HIV disease and, furthermore, infection with HIV-1 increases the risk of reactivation or reinfection with MTb. In this study, we show that host-specific recall responses to one pathogen, MTb, has a direct effect upon the regulation of a second pathogen, HIV-1. Using cells from immunocompetent former tuberculosis (TB) patients who displayed either a persistently positive (responsive) or negative (anergic), delayed-type hypersensitivity (DTH) reaction to intradermal injection of purified protein derivative (PPD), we investigated the effect of recall Ags to MTb upon the replication of HIV-1 primary isolates in vitro. We show that HIV-1 replication of a T cell-tropic isolate was significantly impaired in MTb-stimulated PBMC from PPD-anergic donors. Furthermore, these donors displayed a significant increase in CD8⁺ T cells and IL-10 levels and lower levels of IL-2 and TNF- relative to PPD-responsive donors in response to PPD stimulation. Strikingly, CD8⁺ T cell depletion and blocking of IL-10 significantly increased HIV-1 replication in these PPD-anergic donors, indicating that an immunosuppressive response to MTb recall Ags inhibits HIV-1 replication in PPD-anergic individuals. Therefore, immunotherapeutic approaches aimed at recapitulating Ag-specific MTb anergy in vivo could result in novel and effective approaches to inhibit HIV-1 disease progression in MTb/HIV-1 coinfection.

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