Development of Vγ2Vδ2⁺T Cell Responses during Active Mycobacterial Coinfection of Simian Immunodeficiency Virus–Infected Macaques Requires Control of Viral Infection and Immune Competence of CD4⁺T Cells

Abstract

Vgamma2Vdelta2+ T cells play a role in antimicrobial responses. It is unknown whether adaptive Vgamma2Vdelta2+ T cell responses during active mycobacterial coinfection of human immunodeficiency virus-infected humans can be generated during effective antiretroviral treatment. Here, simian immunodeficiency virus (SIV)mac-infected macaques previously exposed to bacille Calmette-Guerin (BCG) were reinfected with BCG, were treated either with tenofovir or tenofovir plus indinavir, and were assessed for the development of Vgamma2Vdelta2+ T cell responses during active BCG coinfection. A restored capacity of Vgamma2Vdelta2+ T cells to undergo major expansions and pulmonary migration during active BCG coinfection was detected after simultaneous BCG reinfection and treatment with tenofovir of the SIVmac-infected macaques. Interestingly, a restored expansion of Vgamma2Vdelta2+ T cells in the SIVmac/BCG-coinfected macaques was detectable, even though antiretroviral treatment was initiated 1 month after BCG reinfection. Importantly, the restored expansion of Vgamma2Vdelta2+ T cells coincided with increases in numbers of purified protein derivative-specific interferon- gamma -producing CD4+ T cells and increases in the magnitude of their proliferative responses. In contrast, the SIVmac-infected control macaques exhibited diminished responses of Vgamma2Vdelta2+ T cells and mycobacterium-specific CD4+ T cells during active BCG coinfection. Our results suggest that the development of adaptive immune responses of phosphoantigen-specific Vgamma2Vdelta2+ T cells during active mycobacterium/HIV coinfection requires control of viral infection and immune competence of peptide-specific CD4+ T cells.

Tuberculosis-Associated Immune Restoration Syndrome in HIV-1-Infected Patients Involves Tuberculin-Specific CD4 Th1 Cells and KIR-Negative γδ T Cells

“…Similarly, the maturation/activation status of DC, as measured by the level of membrane CD83/CD86 expression, did not differ (Table II), nor did the number of peripheral CD14 ϩ monocytes. Membrane expression of TLR-2, as shown by the MFI, also did not differ between IRS and non-IRS patients on both monocytes (MFI, 30 (IQR, 17-47) vs 31 (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)) and mDC (MFI, 11 (IQR, 5-20) vs 9 (6 -18); Table II).…”

“…Gioia et al (28) showed the quantitative and qualitative restoration of V␦2 ϩ effector memory T cells after TB control. Shen et al (29) have already shown a recovery after HAART of immune responses directed against mycobacterial phosphoantigens, at the same time that the number of tuberculin-specific IFN-␥-producing CD4 T cells increases in bacillus Calmette-Guérin-SIV coinfected monkeys receiving antiretrovirals. In this paper, we add to this body of knowledge the recovery of effector V␦2 ϩ TCR␥␦ T cells during IRS, a finding that supports the involvement of these cells in the inflammatory syndrome.…”

“…They are quantitatively and functionally impaired by both HIV-1 (24) and Mtb infection (25), which create an imbalance between the V␦1 and the normally predominant V␦2 ϩ subsets (26) and V␦2 ϩ anergy (27,28). After HAART and anti-TB treatment, these defects, already associated with inflammatory syndromes in SIV-infected macaques (29), recover, except for the amplification of the V␦1 ϩ population (30). Moreover, the TCR␥␦ T cell effector function is known to be modulated by inhibitory and activating MHC class-I ligand receptors that belong to the NK receptor family.…”

Immune Distribution and Localization of Phosphoantigen-Specific Vγ2Vδ2 T Cells in Lymphoid and Nonlymphoid Tissues inMycobacterium tuberculosisInfection

“…Enzyme-linked immunospot assays for phosphoantigen-specific gamma interferon (IFN-␥)-producing V␥2V␦2 T cells were done as previously described (13,17). The phosphoantigen isopentenyl pyrophosphate was purchased from Sigma (St. Louis, MO) and used at a working concentration of 15 m/liter.…”

NSOM/QD-based nanoscale immunofluorescence imaging of antigen-specific T-cell receptor responses during an in vivo clonal Vγ2Vδ2 T-cell expansion

“…22 PBLs were stimulated using the HMBPP (10 ng/mL), stained intracellularly for interferon-␥ (IFN␥) and perforin, and analyzed by flow cytometry for IFN␥ or perforin-positive V␥2V␦2 T cells. Briefly, PMA and ionomycin (positive control) or media alone (negative control) are added to 10 6 peripheral blood mononuclear cells/200 L media/tube.…”