Expression of the integrin alpha Ebeta 7 identifies unique subsets of CD25+ as well as CD25- regulatory T cells.
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.
Lehmann
Joachim
J
Experimentelle Rheumatologie, Universitätsklinikum Charité, Humboldt-Universität, c/o Deutsches Rheumaforschungszentrum, 10117 Berlin, Germany.
Huehn
Jochen
J
de la Rosa
Maurus
M
Maszyna
Frank
F
Kretschmer
Ute
U
Krenn
Veit
V
Brunner
Monika
M
Scheffold
Alexander
A
Hamann
Alf
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002455:Cell Division; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D006706:Homeostasis; D016023:Integrins / Q000096:biosynthesis* / Q000737:chemistry*; D007371:Interferon-gamma / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets / Q000145:classification*; D013601:T-Lymphocytes / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*; D013997:Time Factors
D016207:Cytokines; D016023:Integrins; D015375:Receptors, Interleukin-2; C070709:integrin alphaEbeta7; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens