Objective: To investigate immune responses of peptide-specific CD4+ and CD8+ T cells, and nonpeptide-specific Vγ2Vδ2+ T cells during clinical quiescence of latent Mycobacterium tuberculosis coinfection in HIV-1-infected humans. Methods: One hundred HIV-1-infected individuals who had HIV infection only [HIV+tuberculosis-(TB-)], latent Mycobacterium tuberculosis coinfection (HIV + LTB), LTB), or active tuberculosis (HIV+ TB) were recruited to measure mycobacterium purified protein derivative (PPD)-specific IFNγ+ CD4+ and CD8+ T cells, and phosphoantigen HMBPP-specific IFNγ+ Vγ2Vδ2+ T cells using enzyme-linked immunospot and intracellular cytokine staining assays. Results: Both HIV + TB and HIV + LTB groups had low levels of PPD-specific IFNγ+ CD4+ T cells regardless of CD4+ peripheral blood lymphocytes counts. However, numbers of PPD-specific IFNγ+ CD8+ T cells in the HIV + LTB group were significantly greater than those in the HIV + TB group. Surprisingly, numbers of phosphoantigen hydroxy-3-methyl-but-2-enyl pyrophosphate-specific IFNγ+ Vγ2Vδ2+ T cells in the HIV + LTB group were much greater than those in the HIV + TB group (P < 0.001). This difference was present in the subgroups of HIV + LTB whatever the levels of CD4+ T-cell counts more than 200/μl or less than 200/μl. Numbers of hydroxy-3-methyl-but-2-enyl pyrophosphate-specific IFNγ+ Vγ2Vδ2+ T cells were even five times greater than those of PPD-specific IFNγ+ CD8 T cells within the HIV + LTB group. Conclusion: Potent immune responses of hydroxy-3-methyl-but-2-enyl pyrophosphate-specific IFNγ+ Vγ2Vδ2+ T cells and PPD-specific IFNγ+ CD8+ T cells were detected in HIV + LTB persons but not HIV + TB patients. The robust immune responses of Vγ2Vδ2+ and CD8+ T effector cells were associated with the latent stage of Mycobacterium tuberculosis coinfection in HIV-1-infected humans. © 2008 Wolters Kluwer Health Lippincott Williams & Wilkins.