β2 microglobulin knockout mice are resistant to lethal intraabdominal sepsis

β2 microglobulin knockout (β2M^-/-) mice lack CD8⁺ T and natural killer T cells. We hypothesized that β2M^-/- mice are resistant to lethal intraabdominal sepsis. To test this hypothesis, mortality, cytokine production, and physiologic function were assessed in β2M^-/- mice during sepsis caused by cecal ligation and puncture (CLP). β2M^-/- mice survived significantly longer than wild-type mice after CLP but ultimately exhibited 100% mortality. Treatment of β2M^-/- mice with anti-asialoGM1 to deplete natural killer cells conferred greater than 70% long-term survival. Compared with wild-type mice, β2M^-/- 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 β2M^-/- 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 β2M^-/- 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.