Colitogenic Th1 cells are present in the antigen-experienced T cell pool in normal mice: control by CD4+ regulatory T cells and IL-10.
CD4(+) regulatory T cells have been shown to prevent intestinal inflammation; however, it is not known whether they act to prevent the priming of colitogenic T cells or actively control these cells as part of the memory T cell pool. In this study, we describe the presence of colitogenic Th1 cells within the CD4(+)CD45RB(low) population. These pathogenic cells enrich within the CD25(-) subset and are not recent thymic emigrants. CD4(+)CD45RB(low) cells from germfree mice were significantly reduced in their ability to transfer colitis to immune deficient recipients, suggesting the presence of commensal bacteria in the donor mice drives colitogenic T cells into the Ag-experienced/memory T cell pool. This potentially pathogenic population of Ag-experienced T cells is subject to T cell-mediated regulation in vivo by both CD4(+)CD25(+) and CD4(+)CD25(-) cells in an IL-10-dependent manner. Furthermore, administration of an anti-IL-10R mAb to unmanipulated adult mice was sufficient to induce the development of colitis. Taken together, these data indicate that colitogenic Th1 cells enter into the Ag-experienced pool in normal mice, but that their function is controlled by regulatory T cells and IL-10. Interestingly, IL-10 was not absolutely required for CD4(+)CD25(+) T cell-mediated inhibition of colitis induced by transfer of naive CD4(+)CD45RB(high) cells, suggesting a differential requirement for IL-10 in the regulation of naive and Ag-experienced T cells.
Asseman
Chrystelle
C
La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
Read
Simon
S
Powrie
Fiona
F
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D005856:Germ-Free Life; D007156:Immunologic Memory / Q000235:genetics; D007274:Injections, Intraperitoneal; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007399:Interphase / Q000235:genetics / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016513:Mice, SCID; D018123:Receptors, Interleukin / Q000276:immunology; D053701:Receptors, Interleukin-10; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D000911:Antibodies, Monoclonal; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D015375:Receptors, Interleukin-2; D016753:Interleukin-10; D017493:Leukocyte Common Antigens