Identification of a CD4+CD25+ T cell subset committed in vivo to suppress antigen-specific T cell responses without additional stimulation

Naturally occurring CD4(+) regulatory T cells can be identified on the basis of expression of CD25 and suppression of T cell responses in vitro after TCR triggering. Here, we demonstrate that a CD134(+) subset of CD4(+)CD25(+) T cells in naive rats suppresses antigen-specific T cell responses in vitro without additional TCR stimulation. In contrast, CD4(+)CD25(+)CD134(-) regulatory T cells and total CD4(+)CD25(+) regulatory T cells have suppressive activity only during simultaneous activation of responder and regulatory T cells or after in vitro pre-activation. Furthermore CD4(+)CD25(+)CD134(+) T cells have a more activated phenotype than CD4(+)CD25(+)CD134(-) T cells, as based on the expression of CD62L, CD45RC, and MHC class II. We propose that the CD134(+) regulatory T cells contain an in vivo activated and highly suppressive regulatory T cell subset. CD4(+)CD25(+)CD134(+) T cells can be found in several compartments of the immune system, including spleen, lymph nodes, and blood. Interestingly though, the relative amounts of these cells within the CD4(+) population and their CD134 expression levels are highest in mucosa-draining lymph nodes and lowest in blood. This suggests that the presence of CD4(+)CD25(+)CD134(+) T cells indicates sites of active immune suppression.