Antibacterial effect of human V gamma 2V delta 2 T cells in vivo

J Clin Invest. 2001 Nov;108(9):1349-57. doi: 10.1172/JCI13584.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens / metabolism
  • Cell Line
  • Cells, Cultured
  • Cytokines / metabolism
  • Enterobacteriaceae Infections / metabolism
  • Enterobacteriaceae Infections / prevention & control
  • Escherichia coli / metabolism
  • Escherichia coli Infections / metabolism
  • Escherichia coli Infections / prevention & control
  • Humans
  • Interferon-gamma / blood
  • Leukocytes, Mononuclear / metabolism
  • Liver / metabolism
  • Lung / metabolism
  • Mice
  • Mice, SCID
  • Monocytes / metabolism
  • Morganella morganii / metabolism
  • Spectrometry, Fluorescence
  • Spleen / metabolism
  • Staphylococcal Infections / metabolism
  • Staphylococcal Infections / prevention & control
  • Staphylococcus aureus / metabolism
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / physiology*
  • Time Factors
  • Tissue Distribution

Substances

  • Antigens
  • Cytokines
  • Interferon-gamma