Characterization of FOXP3+CD4+ regulatory T cells in Crohn's disease.
FOXP3(+)CD4(+) regulatory T cells (T(R)) have emerged as important regulators of immune responses. The aim of our study was to assess the frequency and functional characteristics of FOXP3(+)CD4(+) T(R) in Crohn's disease (CD). We report that FOXP3(+)CD4(+) T(R) cells are expanded in mucosal lymphoid tissues (lamina propria and MLN) but are decreased in the PB in active CD. Patients treated with thiopurines, but not steroids or anti-TNF-alpha inhibitors, have a lower frequency of PB FOXP3(+)CD4(+) T(R) (7.8+/-2.4% vs. 9.9+/-1.8%, p=0.01). FOXP3(+) cells were localized in the lamina propria (LP), muscularis mucosa and serosa and accumulated in granulomas, whereas in MLN they localize in the T cell rich areas. MLN CD4(+)CD25(+) T cells from both CD and normal intestine efficiently suppress the proliferation of effector CD4(+)CD25(-) T cells. T cell activation of MLN in vitro with anti-CD3 plus anti-CD28 Abs enhances the expression of FOXP3, both at the protein and transcriptional level, which is further enhanced by the addition of TGF-beta. In summary, there is an expansion of FOXP3(+)CD4(+) T(R) cells in mucosal lymphoid tissues in CD; they accumulate in areas of active inflammation, including granulomas and retain potent regulatory activity ex vivo.
Saruta
Masayuki
M
Burns and Allen Research Institute, Division of Gastroenterology and Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA, USA.
Yu
Qi T
QT
Fleshner
Phillip R
PR
Mantel
Pierre-Yves
PY
Schmidt-Weber
Carsten B
CB
Banham
Alison H
AH
Papadakis
Konstantinos A
KA
D049109:Cell Proliferation; D018920:Coculture Techniques; D003424:Crohn Disease / Q000276:immunology*; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005786:Gene Expression Regulation; D006099:Granuloma / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*; D014162:Transfection
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors