Response of lung gammadelta T cells to experimental sepsis in mice.
Gammadelta T cells link innate and adaptive immune systems and may regulate host defence. Their role in systemic inflammation induced by trauma or infection (sepsis) is still obscured. The present study was aimed to investigate functions of lung gammadelta T cells and their response to experimental sepsis. Mice were subjected to caecal ligation and puncture (CLP) to induce sepsis and acute lung injury (ALI), or to the sham operation. Animals were killed 1, 4, and 7 days postoperatively; lungs were examined by histology, and isolated cells were studied by flow cytometry. Absolute number of gammadelta T cells progressively increased in lungs during sepsis, and reached a seven-fold increase at day 7 after CLP (3.84 +/- 0.41 x 10(5)/lung; P = 0.0002 versus sham). A cellular dysfunction was revealed one day after CLP, as manifested by low cytolytic activity (22.3 +/- 7.1%; P < 0.05 versus sham), low interferon-gamma (IFN-gamma; 8.5 +/- 2.5%; P < 0.05 versus control) and interleukin-10 (IL-10) expression, and high tumour necrosis factor-alpha expression (19.5 +/- 1.7%; P < 0.05 versus control). The restoration of cytotoxicity, and increase in IFN-gamma and IL-10 expression was observed at day 7 of CLP-induced sepsis. In summary, our results demonstrate significant progressive accumulation of gammadelta T cells in lungs during CLP-induced ALI. The temporary functional suppression of lung gammadelta T cells found early after CLP may influence the outcome of sepsis, possibly being associated with uncontrolled inflammatory lung damage.
Hirsh
Mark
M
Department of Surgery A and the Laboratory for Shock and Trauma Research, Rambam Medical Center, Haifa, Israel. hirsh@tx.technion.ac.il
Dyugovskaya
Larissa
L
Kaplan
Viktoria
V
Krausz
Michael M
MM
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D007371:Interferon-gamma / Q000096:biosynthesis; D008168:Lung / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D012128:Respiratory Distress Syndrome / Q000276:immunology* / Q000473:pathology; D018805:Sepsis / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D016207:Cytokines; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma