Bacterial-reactive T regulatory cells inhibit pathogenic immune responses to the enteric flora.
We showed previously that cecal bacterial Ag (CBA)-specific CD4(+) T cells induce colitis when transferred into SCID mice. The purpose of this study was to generate and characterize CBA-specific regulatory T cells in C3H/HeJBir (Bir) mice. CD4(+) T cells were stimulated with CBA-pulsed APC in the presence of IL-10 every 10-14 days. After four or more cycles, these T cells produced high levels of IL-10, low levels of IL-4 and IFN-gamma, and no IL-2, consistent with the phenotype of T regulatory-1 (Tr1) cells. Bir Tr1 cells proliferated poorly, but their proliferation was dependent on CD28-B7 interactions and was MHC class II-restricted. Transfer of Bir Tr1 cells into SCID mice did not result in colitis, and cotransfer of Bir Tr1 T cells with pathogenic Bir CD4(+) Th1 cells prevented colitis. Bir Tr1 cells inhibited proliferation and IFN-gamma production of a CBA-specific Th1 cell line in vitro. Such inhibition was partly due to IL-10 and TGFbeta1, but cognate interactions with either APCs or Th1 cells were also involved. Normal intestinal lamina propria CD4(+) T cells had Tr1-like activity when stimulated with CBA-pulsed APCs. We conclude that CD4(+) T cells with the properties of Tr1 cells are present in the intestinal lamina propria and hypothesize that these cells maintain intestinal immune homeostasis to the enteric flora.
Cong
Yingzi
Y
Division of Gastroenterology and Hepatology, University of Alabama, Birmingham 35294, USA.
Weaver
Casey T
CT
Lazenby
Audrey
A
Elson
Charles O
CO
D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000942:Antigens, Bacterial / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D003092:Colitis / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004755:Enterobacteriaceae / Q000276:immunology* / Q000472:pathogenicity*; D018928:Immunity, Mucosal; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology
D000942:Antigens, Bacterial; D016207:Cytokines; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma