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

• Published in: European Journal of Immunology Vol. 36; no. 7; pp. 1729 - 1738
• Main Authors: Tramonti, Daniela, Andrew, Elizabeth M, Rhodes, Kate, Newton, Darren J, Carding, Simon R
• Format: Journal Article
• Language: English
• Published: Germany 01-07-2006
• Subjects: Animals; Cells, Cultured; Chemokines - metabolism; Coculture Techniques; Dose-Response Relationship, Immunologic; Homeostasis - immunology; Listeria monocytogenes; Listeria monocytogenes - immunology; Macrophages - immunology; Macrophages - metabolism; Macrophages - microbiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Antigen, T-Cell, gamma-delta - metabolism; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - microbiology
• ISSN: 0014-2980; 1365-2567
• DOI: 10.1002/eji.200635959

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.