Mice depleted of alphabeta but not gammadelta T cells are resistant to mortality caused by cecal ligation and puncture.

Enoh VT, Lin SH, Lin CY, Toliver-Kinsky T, Murphey ED, Varma TK, Sherwood ER
Shock. 2007 27 (5): 507-19

PMID: 17438456 · DOI:10.1097/SHK.0b013e31802b5d9f

The present study was undertaken to determine whether the mice depleted of alphabeta or gammadelta T cells show resistance to acute polymicrobial sepsis caused by cecal ligation and puncture (CLP). T-cell receptor beta knockout (betaTCRKO) and T-cell receptor delta knockout (deltaTCRKO) mice were used. An additional group of mice was treated with an antibody against the alphabeta T-cell receptor to induce alphabeta T-cell depletion; a subset of alphabeta T cell-deficient mice was also treated with anti-asialoGM1 to deplete natural killer (NK) cells. The mice underwent CLP and were monitored for survival, temperature, acid-base balance, bacterial counts, and cytokine production. The betaTCRKO mice and the wild-type mice treated with anti-beta T-cell receptor (anti-TCRbeta) antibody showed improved survival after CLP compared with wild-type mice. The treatment of alphabeta T cell-deficient mice with anti-asialoGM1further improved survival after CLP, especially when the mice were treated with imipenem. The improved survival observed in alphabeta T cell-deficient mice was associated with less hypothermia, improved acid-base balance, and decreased production of the proinflammatory cytokines interleukin (IL) 6 and macrophage inflammatory protein (MIP) 2. Compared with wild-type controls, the overall survival was not improved in deltaTCRKO mice. The concentrations of IL-6 and MIP-2 in plasma and cytokine mRNA expression in tissues were not significantly different between wild-type and deltaTCRKO mice. These studies indicate that mice depleted of alphabeta but not of gammadelta T cells are resistant to mortality in an acutely lethal model of CLP. The depletion of NK cells caused further survival benefit in alphabeta T cell-deficient mice. These findings suggest that alphabeta T and NK cells mediate or facilitate CLP-induced inflammatory injury.

MeSH Terms (24)

Animals Anti-Bacterial Agents Bacteremia Bacteria Cecum Chemokine CXCL2 Enzyme-Linked Immunosorbent Assay Female Flow Cytometry Imipenem Interleukin-6 Killer Cells, Natural Ligation Mice Mice, Inbred C57BL Mice, Knockout Monokines Punctures Receptors, Antigen, T-Cell, alpha-beta Receptors, Antigen, T-Cell, gamma-delta Sepsis T-Lymphocytes Temperature Time Factors

Connections (1)

This publication is referenced by other Labnodes entities: