Murine IL-17(+) V gamma 4 T lymphocytes accumulate in the lungs and play a protective role during severe sepsis

作者：de Souza Costa Maria Fernanda; Trigo de Negreiros Catarina Bastos; Bornstein Victor Ugarte; Valente Richard Hemmi; Mengel Jose; Henriques Maria das Gracas; Benjamim Claudia Farias; Penido Carmen^*

来源：BMC IMMUNOLOGY, 2015, 16(1): 36.

DOI：10.1186/s12865-015-0098-8

• gamma d T cell
• Interleukin-17
• Chemokines
• Sepsis

Background: Lung inflammation is a major consequence of the systemic inflammatory response caused by severe sepsis. Increased migration of gamma delta T lymphocytes into the lungs has been previously demonstrated during experimental sepsis; however, the involvement of the gamma delta T cell subtype V gamma 4 has not been previously described.
Methods: Severe sepsis was induced by cecal ligation and puncture (CLP; 9 punctures, 21G needle) in male C57BL/6 mice. gamma delta and V gamma 4 T lymphocyte depletion was performed by 3A10 and UC3-10A6 mAb i.p. administration, respectively. Lung infiltrating T lymphocytes, IL-17 production and mortality rate were evaluated.
Results: Severe sepsis induced by CLP in C57BL/6 mice led to an intense lung inflammatory response, marked by the accumulation of gamma delta T lymphocytes (comprising the V gamma 4 subtype). gamma delta T lymphocytes present in the lungs of CLP mice were likely to be originated from peripheral lymphoid organs and migrated towards CCL2, CCL3 and CCL5, which were highly produced in response to CLP-induced sepsis. Increased expression of CD25 by V gamma 4 T lymphocytes was observed in spleen earlier than that by alpha beta T cells, suggesting the early activation of V gamma 4 T cells. The V gamma 4 T lymphocyte subset predominated among the IL-17(+) cell populations present in the lungs of CLP mice (unlike V gamma 1 and alpha beta T lymphocytes) and was strongly biased toward IL-17 rather than toward IFN-gamma production. Accordingly, the in vivo administration of anti-V gamma 4 mAb abrogated CLP-induced IL-17 production in mouse lungs. Furthermore, anti-V gamma 4 mAb treatment accelerated mortality rate in severe septic mice, demonstrating that V gamma 4 T lymphocyte play a beneficial role in host defense.
Conclusions: Overall, our findings provide evidence that early-activated V gamma 4 T lymphocytes are the main responsible cells for IL-17 production in inflamed lungs during the course of sepsis and delay mortality of septic mice.

• 出版日期2015-6-3