Foxp3-expressing CD103+ regulatory T cells accumulate in dendritic cell aggregates of the colonic mucosa in murine transfer colitis.
Little is known of the anatomical compartmentalization of colitogenic or regulatory T-cell responses in the murine transfer colitis model. Therefore, we analyzed the putative function of large intestinal dendritic cell (DC) aggregates, to which donor CD4+ T cells selectively home before colitis becomes manifest. The co-stimulatory molecules MHC-II, CD40, CD80, and CD86 were expressed in DC aggregates. IL-23 was primarily absent from DC aggregates at all stages of disease but was expressed at high levels in the severely inflamed lamina propria. Interferon-gamma was up-regulated in the lamina propria during early and advanced disease, whereas in DC aggregates it was detectable to a significant degree only in fully developed colitis. In contrast, Foxp3, a marker of regulatory T cells, was expressed in DC aggregates on T-cell transfer, coinciding with the appearance of CD103+ CD25- T cells in these clusters. Foxp3 was enriched in the CD103+ T-cell fraction isolated from the lamina propria of diseased mice. T-cell grafts depleted of CD103+ T cells generated similar numbers of colonic CD103+ T cells as unfractionated T cells. We conclude that DC aggregates are structures involved in the expansion and/or differentiation of CD103+ CD25- CD4+ Foxp3-expressing regulatory T cells.
Leithäuser
Frank
F
Department of Pathology, University of Ulm, Albert Einstein Allee 11, 89081 Ulm, Germany. frank.leithaeuser@medizin.uni-ulm.de
Meinhardt-Krajina
Tamara
T
Fink
Kerstin
K
Wotschke
Beate
B
Möller
Peter
P
Reimann
Jörg
J
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D003092:Colitis / Q000378:metabolism / Q000473:pathology*; D003106:Colon / Q000166:cytology*; D003713:Dendritic Cells / Q000166:cytology*; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D039001:Integrin alpha Chains / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*
D015703:Antigens, CD; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D039001:Integrin alpha Chains; C091367:alpha E integrins; D049452:Green Fluorescent Proteins