Format

Send to

Choose Destination
See comment in PubMed Commons below
Lab Invest. 2004 Dec;84(12):1655-65.

Mice depleted of CD8+ T and NK cells are resistant to injury caused by cecal ligation and puncture.

Author information

1
Department of Anesthesiology, The University of Texas Medical Branch, Shriners Hospital for Children, Galveston, TX 77555-0591, USA. ersherwo@utmb.edu

Abstract

We previously showed that beta 2 microglobulin knockout mice depleted of NK cells by treatment with anti-asialoGM1 (beta2MKO/alphaAsGM1 mice) are resistant to sepsis caused by cecal ligation and puncture (CLP). beta2MKO mice possess multiple immunological defects including depletion of CD8+ T cells. This study was designed to determine the contribution of CD8+ T and NK cell deficiency to the resistance of beta2MKO/alphaAsGM1 mice to CLP-induced injury. beta2MKO/alphaAsGM1 mice and CD8 knockout mice treated with anti-asialoGM1 (CD8KO/alphaAsGM1 mice) survived significantly longer than wild-type mice following CLP. Improved long-term survival was also observed in wild-type mice rendered CD8+ T/NK cell-deficient by treatment with both anti-CD8alpha and anti-asialoGM1. Blood gas analysis and body temperature measurements showed that CD8+ T and NK cell-deficient mice have significantly reduced metabolic acidosis and less hypothermia compared to control mice at 18 h after CLP. CD8+ T/NK cell-deficient mice also showed an attenuated proinflammatory response as indicated by decreased expression of mRNAs for IL-1, IL-6 and MIP-2 in spleen and heart. IL-6, KC and MIP-2 levels in blood and peritoneal fluid were also significantly decreased CD8+ T/NK cell-deficient mice compared to controls. CD8+ T/NK cell-deficient mice exhibited decreased bacterial concentrations in blood, but not in peritoneal fluid or lung, compared to wild-type controls. These data show that mice depleted of CD8+ T and NK cells exhibit survival benefit, improved physiologic function and an attenuated proinflammatory response following CLP that is comparable to beta2M/alphaAsGM1 mice.

PMID:
15448711
DOI:
10.1038/labinvest.3700184
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group
    Loading ...
    Support Center