Beta 2 microglobulin knockout mice are resistant to lethal intraabdominal sepsis.

Sherwood ER, Lin CY, Tao W, Hartmann CA, Dujon JE, French AJ, Varma TK
Am J Respir Crit Care Med. 2003 167 (12): 1641-9

PMID: 12626348 · DOI:10.1164/rccm.200208-950OC

beta 2 microglobulin knockout (beta2M-/-) mice lack CD8+ T and natural killer T cells. We hypothesized that beta 2M-/- mice are resistant to lethal intraabdominal sepsis. To test this hypothesis, mortality, cytokine production, and physiologic function were assessed in beta 2M-/- mice during sepsis caused by cecal ligation and puncture (CLP). beta 2M-/- mice survived significantly longer than wild-type mice after CLP but ultimately exhibited 100% mortality. Treatment of beta 2M-/- mice with anti-asialoGM1 to deplete natural killer cells conferred greater than 70% long-term survival. Compared with wild-type mice, beta 2M-/- 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 beta 2M-/- 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 beta 2M-/- 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.

MeSH Terms (19)

Adoptive Transfer Animals beta 2-Microglobulin CD8-Positive T-Lymphocytes Cecum Disease Models, Animal Female G(M1) Ganglioside Immunity, Innate Inflammation Killer Cells, Natural Ligation Lymphopenia Mice Mice, Inbred C57BL Mice, Knockout Peritonitis Sepsis Survival Analysis

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