Characterization of T-regulatory cells, induced by immature dendritic cells, which inhibit enteroantigen-reactive colitis-inducing T-cell responses in vitro and in vivo.
Regulatory T (Treg) cells, derived from co-cultures of unfractionated CD4(+) T cells and immature dendritic cells (DC), suppress enteroantigen-induced proliferation of CD4(+) CD25(-) T cells. The DC-induced Treg cells are a mixture of CD25(+) (10-20%) and CD25(-) (80-90%) T cells. However, all the suppressor activity in vitro and in vivo resides in the CD25(+) T-cell subset. The CD25(+) DC-induced Treg cells can inhibit enteroantigen-induced proliferation in vitro through a transwell membrane, and their function does not appear to depend on previous activation. DC-induced CD25(+) Treg cells display a naive phenotype, expressing high levels of CD45RB and l-selectin (CD62L). In addition, the DC-induced Treg cells mediate a stronger suppressive activity than prototype CD25(+) regulatory T cells. The DC-induced Treg cells, and hereof purified CD25(+) and CD25(-) T-cell fractions, were co-injected into severe combined immunodeficiency (SCID) mice with colitis-inducing CD4(+) CD25(-) T cells. Both unfractionated CD4(+) and purified CD25(+) Treg cells fully protected the recipients against the development of colitis. In contrast, co-transfer of fractionated CD25(-) T cells offered no protection against disease development. Enterobacterial antigen-exposed CD4(+) T cells of the protected mice secreted higher levels of interleukin-10 and lower levels of interferon-gamma than the unprotected mice. The present data demonstrate DC-induced CD4(+) CD25(+) Treg cells, which phenotypically and functionally differ from the generally accepted prototype of CD25(+) Treg cells. These data may initiate new procedures for the expansion of Treg cells for clinical use.
Gad
Monika
M
Laboratory of Experimental Immunology, Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Copenhagen, Denmark. m.gad@mami.ku.dk
Kristensen
Nanna N
NN
Kury
Evelyn
E
Claesson
Mogens H
MH
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003092:Colitis / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D015375:Receptors, Interleukin-2 / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000942:Antigens, Bacterial; D016207:Cytokines; D007376:Interleukin-2; D015375:Receptors, Interleukin-2