Antibacterial effect of human Vγ2Vδ2 T cells in vivo
Lisheng Wang, … , Lin Li, Jack F. Bukowski
Lisheng Wang, … , Lin Li, Jack F. Bukowski
Published November 1, 2001
Citation Information: J Clin Invest. 2001;108(9):1349-1357. https://doi.org/10.1172/JCI13584.
View: Text | PDF
Article

Antibacterial effect of human Vγ2Vδ2 T cells in vivo

Abstract

Vγ2Vδ2 cells, a class of T cells found only in primates, are reactive to nonpeptide organophosphate and alkylamine antigens secreted by bacteria and parasites. These cells make up 2-5% percent of human peripheral blood T cells but expand to make up 8–60% of peripheral blood T cells during bacterial and parasitic infections. We show here, using a chimeric severe combined immunodeficiency (SCID) mouse (hu-SCID) model, that human Vγ2Vδ2 T cells mediate resistance to extracellular gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli and Morganella morganii) bacteria, as assessed by survival, body weight, bacterial loads, and histopathology. Surprisingly, this bacterial resistance was evident 1 day after infection, and bacteria were cleared well before γδ T cell expansion was detected 6 days after infection. Decreased resistance in Vδ2 T cell–depleted hu-SCID mice correlated with decreased serum IFN-γ titers. Intravenous treatment of infected, reconstituted hu-SCID mice with pamidronate, a human Vγ2Vδ2 T cell–specific aminobisphosphonate antigen, markedly increased the in vivo antibacterial effect of Vγ2Vδ2 T cells. Therefore, this large pool of antigen-specific, yet immediately reactive memory human Vγ2Vδ2 T cells is likely to be an important mediator of resistance against extracellular bacterial infection and may bridge the gap between innate and acquired immunity.

Authors

Lisheng Wang, Arati Kamath, Hiranmoy Das, Lin Li, Jack F. Bukowski

×

Figure 1

Options: View larger image (or click on image) Download as PowerPoint
Depletion of Vδ2 T cells exacerbated bacterial infection (a–c), whereas ...
Depletion of Vδ2 T cells exacerbated bacterial infection (a–c), whereas live bacterial product augmented the antibacterial effects of Vγ2Vδ2 T cells (d–g). (a) All SCID-beige mice infected with a lethal dose of E. coli (1 × 107 CFUs, administered intraperitoneally) were dead within 2 days, whereas all mice reconstituted with human PBMCs survived this lethal infection. (b) Six of ten SCID-beige mice reconstituted with human PBMCs depleted of Vδ2 T cells died of E. coli infection (3 × 107 CFUs, administered intraperitoneally); in contrast, only one of ten mice receiving mock-depleted PBMCs died. (c) Reconstitution of SCID mice with intraperitoneal PBMCs depleted of Vδ2 T cells resulted in higher bacterial loads in the peritoneal lavages of these mice 5 days after intraperitoneal inoculation of M. morganii (3 × 107 CFUs). (d) SCID mice (n = 5 for each group) reconstituted intraperitoneally with PBMCs pretreated with IBA, a natural Vγ2Vδ2 T cell–specific antigen secreted by bacteria, had lower numbers of bacterial CFUs in the peritoneal lavage (e) less loss of body weight (*P < 0.05), and (f) markedly less liver degeneration than those reconstituted intraperitoneally with medium-pretreated PBMCs 5 days after intraperitoneal infection with 3 × 107 CFUs of M. morganii (×200, hematoxylin and eosin staining). Bottom panel: IBA group. Top panel: medium control. (g) SCID mice reconstituted intraperitoneally with IBA-pretreated PBMCs (IBA) had lower numbers of bacterial CFUs than those receiving medium-pretreated PBMCs (Medium) 5 days after intravenous infection with 3 × 107 CFUs of M. morganii.