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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 naïve 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‐γ 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.