CD4+CD25bright T cells in human intestinal lamina propria as regulatory cells.
It is well known that immune responses in the intestine remain in a state of controlled inflammation, suggesting that not only active suppression by regulatory T cells plays an important role in the normal intestinal homeostasis, but also its dysregulation leads to the development of inflammatory bowel disease. In this study, we demonstrate that the CD4(+)CD25(bright) T cells reside in the human intestinal lamina propria (LP) and functionally retain regulatory activities. All human LP CD4(+) T cells regardless of CD25 expression constitutively expressed CTLA-4, glucocorticoid-induced TNFR family-related protein, and Foxp3 and proliferate poorly. Although LP CD4(+)CD25(-) T cells showed an activated and anergic/memory phenotype, they did not retain regulatory activity. In LP CD4(+)CD25(+) T cells, however, cells expressing CD25 at high levels (CD4(+)CD25(bright)) suppressed the proliferation and various cytokine productions of CD4(+)CD25(-) T cells. LP CD4(+)CD25(bright) T cells by themselves produced fewer amounts of IL-2, IFN-gamma, and IL-10. Interestingly, LP CD4(+)CD25(bright) T cells with regulatory T activity were significantly increased in patients with active inflammatory bowel disease. These results suggest that CD4(+)CD25(bright) T cells found in the normal and inflamed intestinal mucosa selectively inhibit the host immune response and therefore may contribute to the intestinal immune homeostasis.
Makita
Shin
S
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Kanai
Takanori
T
Oshima
Shigeru
S
Uraushihara
Koji
K
Totsuka
Teruji
T
Sawada
Taisuke
T
Nakamura
Tetsuya
T
Koganei
Kazutaka
K
Fukushima
Tsuneo
T
Watanabe
Mamoru
M
D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D060908:CTLA-4 Antigen; D003093:Colitis, Ulcerative / Q000276:immunology; D003106:Colon / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology; D003424:Crohn Disease / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism; D051858:Forkhead Transcription Factors; D053450:Glucocorticoid-Induced TNFR-Related Protein; D006801:Humans; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000276:immunology / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines; D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053450:Glucocorticoid-Induced TNFR-Related Protein; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C491405:TNFRSF18 protein, human