¹Department of Anesthesiology, The University of Texas Medical Branch, Shriners Hospital for Children, Galveston, TX, USA

Correspondence: Dr ER Sherwood, MD, PhD, Department of Anesthesiology, The University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555-0591, USA. E-mail: ersherwo@utmb.edu

Received 18 July 2004; Accepted 19 August 2004; Published online 27 September 2004.

Abstract

We previously showed that beta 2 microglobulin knockout mice depleted of NK cells by treatment with anti-asialoGM1 (2MKO/AsGM1 mice) are resistant to sepsis caused by cecal ligation and puncture (CLP). 2MKO 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 2MKO/AsGM1 mice to CLP-induced injury. 2MKO/AsGM1 mice and CD8 knockout mice treated with anti-asialoGM1 (CD8KO/AsGM1 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-CD8 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 2M/AsGM1 mice.