Evidence for the opposing roles of different γδ T cell subsets in macrophage homeostasis

Daniela Tramonti, Elizabeth M Andrew, Kate Rhodes, Darren J Newton, Simon R Carding

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

To ensure invading pathogens are eliminated with minimal damage to host tissues it is essential that macrophage activation be tightly regulated. Previously we demonstrated that a subset of gammadelta T cells (Vgamma1(+)) contributes to resolving pathogen-induced immune responses by killing activated macrophages. However, the exaggerated macrophage response seen in infected Vgamma1(+) T cell-deficient mice suggests that gammadelta T cells play a broader role in macrophage homeostasis and other subsets might promote macrophage activation. Using a macrophage:gammadelta T cell co-culture system we have shown that gammadelta T cells increase the activity of macrophages activated in vivo by Listeria monocytogenes infection. In a dose-dependent manner, gammadelta T cells up-regulated production of cytokines (TNF-alpha, IL-6, IL-10) and chemokines (MIP-1alpha, MIP-1beta) by Listeria-elicited macrophages. The ability to increase macrophage cytokine production was prominent among Vgamma4(+) gammadelta T cells. Reciprocally, Vgamma4(+) gammadelta T cells were activated by Listeria-elicited macrophages, resulting in production of the anti-inflammatory cytokine, IL-10. gammadelta T cell adoptive transfer experiments showed that Vgamma4(+) T cells protected TCRdelta(-/-) mice against Listeria-induced liver injury and necrosis. These findings identify distinct and non-overlapping roles for gammadelta T cell subsets in regulating macrophage function during pathogen-induced immune responses.
Original languageEnglish
Pages (from-to)1729-1738
Number of pages10
JournalEuropean Journal of Immunology
Volume36
Issue number7
DOIs
Publication statusPublished - Jul 2006

Keywords

  • Animals
  • Cells, Cultured
  • Chemokines
  • Coculture Techniques
  • Dose-Response Relationship, Immunologic
  • Homeostasis
  • Listeria monocytogenes
  • Macrophages
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Antigen, T-Cell, gamma-delta
  • T-Lymphocyte Subsets

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