Expression of the integrin alpha Ebeta 7 identifies unique subsets of CD25+ as well as CD25- regulatory T cells

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 99; no. 20; pp. 13031 - 13036
• Main Authors: Lehmann, Joachim, Huehn, Jochen, de la Rosa, Maurus, Maszyna, Frank, Kretschmer, Ute, Krenn, Veit, Brunner, Monika, Scheffold, Alexander, Hamann, Alf
• Format: Journal Article
• Language: English
• Published: United States 01.10.2002
• Subjects: Animals; CD4-Positive T-Lymphocytes - metabolism; Cell Division; Cell Separation; Cytokines - biosynthesis; Female; Flow Cytometry; Homeostasis; Integrins - biosynthesis; Integrins - chemistry; Interferon-gamma - metabolism; Leukocyte Common Antigens - metabolism; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, SCID; Receptors, Interleukin-2 - biosynthesis; T-Lymphocyte Subsets - classification; T-Lymphocytes - metabolism; Th2 Cells - metabolism; Time Factors
• ISSN: 0027-8424

Regulatory CD25(+)CD4(+) T cells are considered as important players in T cell homeostasis and self-tolerance. Here we report that the integrin alpha(E)beta(7), which recognizes epithelial cadherin, identifies the most potent subpopulation of regulatory CD25(+) T cells. Strikingly, CD25-negative alpha(E)+CD4(+) T cells displayed regulatory activity. Both alpha(E)+ subsets, CD25(+) and CD25(-), express CTLA-4, suppress T cell proliferation in vitro, and protect mice from colitis in the severe combined immunodeficient model (SCID) in vivo. Whereas alpha(E)+CD25(+) T cells produce almost no cytokines, alpha(E)+CD25(-) T cells represent a unique subset in which high IL-2, IFN-gamma and T helper 2-cytokine production is linked with suppressive function. Thus, the integrin alpha(E)beta(7) can be regarded as a novel marker for subsets of highly potent, functionally distinct regulatory T cells specialized for crosstalk with epithelial environments.