Murine IL-17+ Vγ4 T lymphocytes accumulate in the lungs and play a protective role during severe sepsis

Maria Fernanda de Souza Costa, Catarina Bastos Trigo de Negreiros, Victor Ugarte Bornstein, Richard Hemmi Valente, José Mengel, Maria das Graças Henriques, Claudia Farias Benjamim, Carmen Penido

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25 Scopus citations

Abstract

Background: Lung inflammation is a major consequence of the systemic inflammatory response caused by severe sepsis. Increased migration of γδ T lymphocytes into the lungs has been previously demonstrated during experimental sepsis; however, the involvement of the γδ T cell subtype Vγ4 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. γδ and Vγ4 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 γδ T lymphocytes (comprising the Vγ4 subtype). γδ 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 Vγ4 T lymphocytes was observed in spleen earlier than that by αβ T cells, suggesting the early activation of Vγ4 T cells. The Vγ4 T lymphocyte subset predominated among the IL-17+ cell populations present in the lungs of CLP mice (unlike Vγ1 and αβ T lymphocytes) and was strongly biased toward IL-17 rather than toward IFN-γ production. Accordingly, the in vivo administration of anti-Vγ4 mAb abrogated CLP-induced IL-17 production in mouse lungs. Furthermore, anti-Vγ4 mAb treatment accelerated mortality rate in severe septic mice, demonstrating that Vγ4 T lymphocyte play a beneficial role in host defense. Conclusions: Overall, our findings provide evidence that early-activated Vγ4 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.

Original languageEnglish
Article number36
JournalBMC Immunology
Volume16
Issue number1
DOIs
StatePublished - 3 Jun 2015

Keywords

  • Chemokines
  • Interleukin-17
  • Sepsis
  • γδ T cell

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