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

Citation
Ls. Wang et al., Antibacterial effect of human V gamma 2V delta 2 T cells in vivo, J CLIN INV, 108(9), 2001, pp. 1349-1357
Citations number
53
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Medical Research General Topics
Journal title
JOURNAL OF CLINICAL INVESTIGATION
ISSN journal
0021-9738 → ACNP
Volume
108
Issue
9
Year of publication
2001
Pages
1349 - 1357
Database
ISI
SICI code
0021-9738(200111)108:9<1349:AEOHVG>2.0.ZU;2-5
Abstract
V gamma 2V delta2 cells, a class of T cells found only in primates, are rea ctive to nonpeptide organophosphate and alkylamine antigens secreted by bac teria and parasites. These cells make up 2-5% percent of human peripheral b lood 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 delta2 T cells mediate resistance to extracellular gram-positive (Staphy lococcus aureus) and gram-negative (Escherichia coli and Morganella morgani i) bacteria, as assessed by survival, body weight, bacterial loads, and his topathology. Surprisingly, this bacterial resistance was evident 1 day afte r infection, and bacteria were cleared welt before gamma delta T cell expan sion was detected 6 days after infection. Decreased resistance in V delta2 T cell-depleted hu-SCID mice correlated with decreased serum IFN-gamma tite rs. Intravenous treatment of infected, reconstituted hu-SCID mice with pami dronate, a human V gamma 2V delta2 T cell-specific aminobisphosphonate anti gen, markedly increased the in vivo antibacterial effect of V gamma 2V delt a2 T cells. Therefore, this large pool of antigen-specific, yet immediately reactive memory human V gamma 2V delta2 T cells is likely to be an importa nt mediator of resistance against extracellular bacterial infection and may bridge the gap between innate and acquired immunity.