CD4-expressing cells are early mediators of the innate immune system during sepsis.

Abstract

It is well established that the immune response to sepsis is mediated by leukocytes associated with the innate immune system. However, there is an emerging view that T lymphocytes can also mediate this response. Here, we observed a significant depletion of both CD4 and CD8 T cells in human patients after blunt trauma. To determine what effect the loss of these cells may have during a subsequent infection, we obtained CD4- and CD8-deficient mice and subjected them to cecal ligation and puncture (CLP). We observed that CD4 knockout (KO) mice showed increased CLP-induced mortality compared with CD8-deficient and wild-type (WT) mice especially within the first 30 h of injury. CD4 KO mice also exhibited significantly increased IL-6 concentrations after the CLP. The CD4 KO mice had an increased concentration of bacteremia as compared with WT mice. Antibiotic treatment decreased mortality in the CD4 KO mice as compared with no changes in the wild mice after CLP. Neutrophils isolated from septic CD4 KO mice showed decreased spontaneous oxidative burst compared with neutrophils taken from septic controls. We examined the role of IFN-gamma by using mice deficient in this cytokine and found these mice to have significantly higher mortality as compared with WT mice. Finally, we detected a 2-fold increase in CD11b+ cells that exhibited intracellular IFN-gamma staining in the peritoneum of WT mice after CLP. The data suggest that CD4+ cells may facilitate the early clearance of bacteria by regulating neutrophils function possibly through an IFN-gamma-dependent mechanism.

• Authors: André Martignoni, Johannes Tschöp, Holly S Goetzman, Lisa G Choi, Maria D Reid, Jay A Johannigman, Alex B Lentsch, Charles C Caldwell
• Journal: Shock (Augusta, Ga.) (Shock) Vol. 29 Issue 5 Pg. 591-7 (May 2008) ISSN: 1073-2322 [Print] United States
• PMID: 17885647 (Publication Type: Journal Article)

Chemical References

• CD11b Antigen
• Interleukin-6
• Interferon-gamma

Topics

• Animals
• CD11b Antigen (biosynthesis)
• CD4-Positive T-Lymphocytes (metabolism)
• CD8-Positive T-Lymphocytes (metabolism)
• Enzyme-Linked Immunosorbent Assay
• Gene Expression Regulation
• Humans
• Interferon-gamma (metabolism)
• Interleukin-6 (biosynthesis)
• Male
• Mice
• Mice, Knockout
• Respiratory Burst
• Sepsis (blood)
• Wounds and Injuries (blood)