Antibacterial effect of human V gamma 2V delta 2 T cells in vivo.
V gamma 2V delta 2 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 V gamma 2V delta 2 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 gamma delta T cell expansion was detected 6 days after infection. Decreased resistance in V delta 2 T cell-depleted hu-SCID mice correlated with decreased serum IFN-gamma titers. Intravenous treatment of infected, reconstituted hu-SCID mice with pamidronate, a human V gamma 2V delta 2 T cell-specific aminobisphosphonate antigen, markedly increased the in vivo antibacterial effect of V gamma 2V delta 2 T cells. Therefore, this large pool of antigen-specific, yet immediately reactive memory human V gamma 2V delta 2 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.
Wang
L
L
Lymphocyte Biology Section, Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Kamath
A
A
Das
H
H
Li
L
L
Bukowski
J F
JF
D000818:Animals; D000941:Antigens / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004756:Enterobacteriaceae Infections / Q000378:metabolism / Q000517:prevention & control; D004926:Escherichia coli / Q000378:metabolism; D004927:Escherichia coli Infections / Q000378:metabolism / Q000517:prevention & control; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D009000:Monocytes / Q000378:metabolism; D020613:Morganella morganii / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013154:Spleen / Q000378:metabolism; D013203:Staphylococcal Infections / Q000378:metabolism / Q000517:prevention & control; D013211:Staphylococcus aureus / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000502:physiology*; D013997:Time Factors; D014018:Tissue Distribution
D000941:Antigens; D016207:Cytokines; D007371:Interferon-gamma