CD4+CD25+ T cells regulate colonic localization of CD4 T cells reactive to a microbial antigen.
BACKGROUND
In patients with inflammatory bowel diseases, T-cell activation driven by microflora has been implicated as a mechanism causing clonal expansion and infiltration of CD4+ T cells in colonic lamina propria (LP). We explored a regulatory mechanism preventing infiltration of CD4+ T cells specific to a microbe-associated antigen in the gut.


METHODS
SCID mice were reconstituted with CD4+ T cells specific to ovalbumin (OVA) and were orally administered with Escherichia coli engineered to produce OVA.


RESULTS
OVA-specific CD4+ T cells (KJ1-26+) were recruited to colonic LP in an Ag-dependent manner, which was inhibited by adoptive transfer of naturally occurring CD4+CD25+ T (Treg) cells. KJ1-26+ T cells and Treg cells are localized preferentially to the colonic follicles that contain dendritic cells. In mice given Treg cells, LP CD4+ T cells showed a decrease in proliferative and interferon gamma response and an increase in transforming growth factor beta1 response to OVA stimulation. Treg cells inhibited both antigenic activation of effector CD4+ T cells and class II/CD80/CD86 up-regulation of dendritic cells.


CONCLUSIONS
: Treg cells suppress recruitment of CD4+ T cells specific to a microbe-associated antigen to LP, which was associated with colocalization of effector CD4+ T cells and Treg cells in colonic follicles.
Watanabe
Tomohiro
T
Department of Clinical Bio-regulatory Science, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Japan.
Yamori
Masashi
M
Kita
Toru
T
Chiba
Tsutomu
T
Wakatsuki
Yoshio
Y
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement; D049109:Cell Proliferation; D003092:Colitis / Q000276:immunology* / Q000662:veterinary; D003106:Colon / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D015375:Receptors, Interleukin-2 / Q000276:immunology*
D000942:Antigens, Bacterial; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma