CD4+CD25+ T(R) cells suppress innate immune pathology through cytokine-dependent mechanisms.
CD4(+)CD25(+) regulatory T (T(R)) cells can inhibit a variety of autoimmune and inflammatory diseases, but the precise mechanisms by which they suppress immune responses in vivo remain unresolved. Here, we have used Helicobacter hepaticus infection of T cell-reconstituted recombination-activating gene (RAG)(-/-) mice as a model to study the ability of CD4(+)CD25(+) T(R) cells to inhibit bacterially triggered intestinal inflammation. H. hepaticus infection elicited both T cell-mediated and T cell-independent intestinal inflammation, both of which were inhibited by adoptively transferred CD4(+)CD25(+) T(R) cells. T cell-independent pathology was accompanied by activation of the innate immune system that was also inhibited by CD4(+)CD25(+) T(R) cells. Suppression of innate immune pathology was dependent on T cell-derived interleukin 10 and also on the production of transforming growth factor beta. Thus, CD4(+)CD25(+) T(R) cells do not only suppress adaptive T cell responses, but are also able to control pathology mediated by innate immune mechanisms.
Maloy
Kevin J
KJ
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, United Kingdom. kevin.maloy@path.ox.ac.uk
Salaun
Laurence
L
Cahill
Rachel
R
Dougan
Gordon
G
Saunders
Nigel J
NJ
Powrie
Fiona
F
D019264:Adoptive Transfer; D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism*; D016207:Cytokines / Q000276:immunology*; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016753:Interleukin-10 / Q000276:immunology; D007422:Intestines / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000276:immunology
D015704:CD4 Antigens; D016207:Cytokines; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta; D016753:Interleukin-10