β2 microglobulin knockout mice are resistant to lethal intraabdominal sepsis

Edward R. Sherwood, Cheng Y. Lin, Weike Tao, Christopher A. Hartmann, Jay E. Dujon, Andrew J. French, Tushar K. Varma

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1641-1649
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume167
Issue number12
DOIs
StatePublished - Jun 15 2003

Fingerprint

Knockout Mice
Sepsis
Punctures
Ligation
Natural Killer T-Cells
Mortality
Cytokines
Adoptive Transfer
Acidosis
Hypothermia
Natural Killer Cells
Immunoglobulin G
Antibodies
Therapeutics

Keywords

  • CD8 T lymphocytes
  • Natural killer cells
  • Septic shock

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

β2 microglobulin knockout mice are resistant to lethal intraabdominal sepsis. / Sherwood, Edward R.; Lin, Cheng Y.; Tao, Weike; Hartmann, Christopher A.; Dujon, Jay E.; French, Andrew J.; Varma, Tushar K.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 167, No. 12, 15.06.2003, p. 1641-1649.

Research output: Contribution to journalArticle

Sherwood, Edward R. ; Lin, Cheng Y. ; Tao, Weike ; Hartmann, Christopher A. ; Dujon, Jay E. ; French, Andrew J. ; Varma, Tushar K. / β2 microglobulin knockout mice are resistant to lethal intraabdominal sepsis. In: American Journal of Respiratory and Critical Care Medicine. 2003 ; Vol. 167, No. 12. pp. 1641-1649.
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