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 activityin vitroandin vivoresides in the CD25⁺ T-cell subset. The CD25⁺ DC-induced Treg cells can inhibit enteroantigen-induced proliferationin vitrothrough 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 andl-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. [ABSTRACT FROM AUTHOR]