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.
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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

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Treatment with aminobisphosphonate antigen but not bisphosphonate in viv...
Treatment with aminobisphosphonate antigen but not bisphosphonate in vivo enhanced the antibacterial effect of PBMCs (a–c); human Vγ2Vδ2 T cells expanded in SCID mice (d, e). SCID mice intraperitoneally reconstituted with PBMCs and treated with intravenous pamidronate (10 mg/kg body weight), a Vγ2Vδ2 T cell–specific aminobisphosphonate antigen, 2 hours after infection with intravenous M. morganii (3 × 107 CFUs), had fewer liver and spleen CFUs than did reconstituted, infected SCID mice treated with etidronate (10 mg/kg body weight), an antigenically inactive bisphosphonate analogue of pamidronate. (a) Four days after infection, SCID mice (n = 5) reconstituted intraperitoneally with PBMCs pretreated with pamidronate had lower numbers of CFUs than those reconstituted with etidronate-pretreated PBMCs 27 hours after intraperitoneal infection with E. coli (5 × 106 CFUs) (b) or 17 hours after infection with S. aureus (2 × 106 CFUs) (c); n = 5 for each group. (d) Flow cytometry profile, and (e) absolute numbers of Vγ2Vδ2 T cells in the peritoneal lavage: Human Vγ2Vδ2 T cells in the peritoneal lavage of SCID mice (n = 5 in each group) reconstituted intraperitoneally with IBA-pretreated PBMCs were expanded by day 7 after intraperitoneal infection with 3 × 107 CFUs of M. morganii (IBA + M. morganii), compared with peritoneal lavage Vγ2Vδ2 T cells from reconstituted SCID mice that were mock-infected (IBA). Each SCID mouse was reconstituted with PBMCs that contained 2.5 × 105 γδ T cells. Data were representative of three experiments.