This Article Full Text Full Text (PDF) All Versions of this Article: 200208-950OCv1 167/12/1641    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sherwood, E. R. Articles by Varma, T. K. Search for Related Content PubMed PubMed Citation Articles by Sherwood, E. R. Articles by Varma, T. K.

ß2 Microglobulin Knockout Mice Are Resistant to Lethal Intraabdominal Sepsis

Department of Anesthesiology, University of Texas Medical Branch, Shriners Hospital for Children, Galveston, Texas

Correspondence and requests for reprints should be addressed to Edward R. Sherwood, M.D., Department of Anesthesiology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0591. E-mail: ersherwo{at}utmb.edu

ß2 microglobulin knockout (ß2M^-/-) mice lack CD8⁺ T and natural killer T cells. We hypothesized that ß2M^-/- mice are resistant to lethal intraabdominal sepsis. To test this hypothesis, mortality, cytokine production, and physiologic function were assessed in ß2M^-/- mice during sepsis caused by cecal ligation and puncture (CLP). ß2M^-/- mice survived significantly longer than wild-type mice after CLP but ultimately exhibited 100% mortality. Treatment of ß2M^-/- mice with anti-asialoGM1 to deplete natural killer cells conferred greater than 70% long-term survival. Compared with wild-type mice, ß2M^-/- mice treated with anti-asialoGM1 produced decreased amounts of proinflammatory cytokines and did not exhibit hypothermia or metabolic acidosis after CLP. Adoptive transfer of CD8⁺ T and natural killer cells into ß2M^-/- mice treated with anti-asialoGM1 re-established CLP-induced mortality. CD8 knockout mice treated with anti-asialoGM1, which are specifically deficient in CD8⁺ T and natural killer cells, exhibited 40% long-term survival after CLP. Furthermore, treatment of wild-type mice with antibodies to CD8 and asialoGM1 conferred a significant survival benefit compared with wild-type mice treated with nonspecific IgG. These findings demonstrate that ß2M^-/- mice treated with anti-asialoGM1 are resistant to CLP-induced mortality and that depletion of CD8⁺ T and natural killer cells largely accounts for the survival benefit observed in these mice.

Key Words: CD8⁺ T lymphocytes • natural killer cells • septic shock

This article has been cited by other articles:

				A. L. Cogen and T. A. Moore {beta}2-Microglobulin-Dependent Bacterial Clearance and Survival during Murine Klebsiella pneumoniae Bacteremia Infect. Immun., January 1, 2009; 77(1): 360 - 366. [Abstract] [Full Text] [PDF]

				A. O. Etogo, J. Nunez, C. Y. Lin, T. E. Toliver-Kinsky, and E. R. Sherwood NK but Not CD1-Restricted NKT Cells Facilitate Systemic Inflammation during Polymicrobial Intra-Abdominal Sepsis J. Immunol., May 1, 2008; 180(9): 6334 - 6345. [Abstract] [Full Text] [PDF]

				D. E. Wesche-Soldato, C.-S. Chung, S. H. Gregory, T. P. Salazar-Mather, C. A. Ayala, and A. Ayala CD8+ T Cells Promote Inflammation and Apoptosis in the Liver after Sepsis: Role of Fas-FasL Am. J. Pathol., July 1, 2007; 171(1): 87 - 96. [Abstract] [Full Text] [PDF]

				V. T. Enoh, C. D. Fairchild, C. Y. Lin, T. K. Varma, and E. R. Sherwood Differential effect of imipenem treatment on wild-type and NK cell-deficient CD8 knockout mice during acute intra-abdominal injury Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2006; 290(3): R685 - R693. [Abstract] [Full Text] [PDF]

				V. T. Enoh, C. Y. Lin, T. K. Varma, and E. R. Sherwood Differential effect of imipenem treatment on injury caused by cecal ligation and puncture in wild-type and NK cell-deficient {beta}2-microgloblin knockout mice Am J Physiol Gastrointest Liver Physiol, February 1, 2006; 290(2): G277 - G284. [Abstract] [Full Text] [PDF]

				W. Tao, V. T. Enoh, C. Y. Lin, W. E. Johnston, P. Li, and E. R. Sherwood Cardiovascular dysfunction caused by cecal ligation and puncture is attenuated in CD8 knockout mice treated with anti-asialoGM1 Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2005; 289(2): R478 - R485. [Abstract] [Full Text] [PDF]

				T. E. Toliver-Kinsky, W. Cui, E. D. Murphey, C. Lin, and E. R. Sherwood Enhancement of Dendritic Cell Production by Fms-Like Tyrosine Kinase-3 Ligand Increases the Resistance of Mice to a Burn Wound Infection J. Immunol., January 1, 2005; 174(1): 404 - 410. [Abstract] [Full Text] [PDF]

				E. Pravinkumar and E. R. Sherwood Balance of Inflammation in Sepsis Am. J. Respir. Crit. Care Med., March 1, 2004; 169(5): 655 - 656. [Full Text]

				W. Tao and E. R. Sherwood {beta}2-Microglobulin knockout mice treated with anti-asialoGM1 exhibit improved hemodynamics and cardiac contractile function during acute intra-abdominal sepsis Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2004; 286(3): R569 - R575. [Abstract] [Full Text] [PDF]

				M. J. Tobin Critical Care Medicine in AJRCCM 2003 Am. J. Respir. Crit. Care Med., January 15, 2004; 169(2): 239 - 253. [Full Text] [PDF]