CD4+CD25+ T Cells Regulate Colonic Localization of CD4 T Cells Reactive to a Microbial Antigen

T Watanabe, M Yamori, T Kita, T Chiba… - Inflammatory bowel …, 2005 - academic.oup.com
T Watanabe, M Yamori, T Kita, T Chiba, Y Wakatsuki
Inflammatory bowel diseases, 2005academic.oup.com
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 …
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 γ response and an increase in transforming growth factor β1 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.
Conclusion
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.
Oxford University Press