Mice depleted of alphabeta but not gammadelta T cells are resistant to mortality caused by cecal ligation and puncture.
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.
Enoh
Victor T
VT
*Departments of Anesthesiology , The University of Texas Medical Branch, Galveston, Galveston, Texas 77555-0591, USA.
Lin
Scott H
SH
Lin
Cheng Y
CY
Toliver-Kinsky
Tracy
T
Murphey
Erle D
ED
Varma
Tushar K
TK
Sherwood
Edward R
ER
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D016470:Bacteremia / Q000188:drug therapy / Q000276:immunology / Q000401:mortality; D001419:Bacteria / Q000187:drug effects / Q000254:growth & development; D002432:Cecum / Q000293:injuries*; D054426:Chemokine CXCL2; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015378:Imipenem / Q000627:therapeutic use; D015850:Interleukin-6 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008026:Ligation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015846:Monokines / Q000378:metabolism; D011677:Punctures; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D018805:Sepsis / Q000188:drug therapy / Q000276:immunology / Q000401:mortality; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013696:Temperature; D013997:Time Factors
D000900:Anti-Bacterial Agents; D054426:Chemokine CXCL2; D015850:Interleukin-6; D015846:Monokines; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015378:Imipenem