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Beta 2 microglobulin knockout mice are resistant to lethal intraabdominal sepsis
Edward R Sherwood1, Cheng Y Lin, Weike Tao
1Department of Anesthesiology, University of Texas Medical Branch, Shriners Hospital for Children, Galveston, TX 77555-0591, USA. ersherwo@utmb.edu
American Journal of Respiratory and Critical Care Medicine
|March 11, 2003
Summary
Beta 2 microglobulin knockout mice showed initial resistance to sepsis but ultimately succumbed. Depleting natural killer cells significantly improved survival in these mice, highlighting their role in sepsis mortality.
Area of Science:
- Immunology
- Sepsis Pathophysiology
Background:
- Beta 2 microglobulin knockout (beta2M-/-) mice lack CD8+ T and natural killer T cells.
- Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, remains a significant clinical challenge.
Purpose of the Study:
- To investigate the role of CD8+ T and natural killer T cells in sepsis-induced mortality using beta2M-/- mice.
- To determine if beta2M-/- mice are resistant to lethal intraabdominal sepsis.
Main Methods:
- Cecal ligation and puncture (CLP) model of sepsis was performed in beta2M-/- and wild-type mice.
- Mortality, cytokine production, and physiological parameters were assessed.
- Natural killer cells were depleted using anti-asialoGM1 antibody treatment.
- Adoptive cell transfer experiments were conducted.
Main Results:
- Beta2M-/- mice exhibited prolonged survival post-CLP but ultimately 100% mortality.
- Anti-asialoGM1 treatment conferred >70% long-term survival in beta2M-/- mice.
- Depletion of natural killer and CD8+ T cells significantly reduced sepsis mortality.
Conclusions:
- Beta 2 microglobulin knockout mice treated with anti-asialoGM1 demonstrate resistance to CLP-induced mortality.
- Depletion of CD8+ T and natural killer cells largely accounts for the survival benefit in this sepsis model.
- These findings underscore the critical roles of CD8+ T and natural killer cells in sepsis pathogenesis.