CD4+CD25bright T cells in human intestinal lamina propria as regulatory cells

J Immunol. 2004 Sep 1;173(5):3119-30. doi: 10.4049/jimmunol.173.5.3119.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD
  • Antigens, Differentiation / immunology
  • Antigens, Differentiation / metabolism
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CTLA-4 Antigen
  • Colitis, Ulcerative / immunology
  • Colon / immunology*
  • Colonic Neoplasms / immunology
  • Crohn Disease / immunology
  • Cytokines / immunology
  • Cytokines / metabolism
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism
  • Forkhead Transcription Factors
  • Glucocorticoid-Induced TNFR-Related Protein
  • Humans
  • Phenotype
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Interleukin-2 / deficiency
  • Receptors, Interleukin-2 / genetics
  • Receptors, Interleukin-2 / metabolism*
  • Receptors, Nerve Growth Factor / immunology
  • Receptors, Nerve Growth Factor / metabolism
  • Receptors, Tumor Necrosis Factor / immunology
  • Receptors, Tumor Necrosis Factor / metabolism


  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Cytokines
  • DNA-Binding Proteins
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Glucocorticoid-Induced TNFR-Related Protein
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-2
  • Receptors, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor
  • TNFRSF18 protein, human