Phenotypic and functional differences in Foxp3+ cells expressing different levels of the IL-2 receptor α-chain CD25 (115.20)

Abstract

Regulatory T cells (Tregs) are key players in tolerance and immune homeostasis. The identification of this unique cell subset was originally established through identification of CD4+ T cells expressing high levels of the IL-2 receptor α-chain CD25. CD4+CD25+ cells from naïve mice are predominantly Tregs. CD4+CD25- cells are predominantly conventional T cells. With the identification of the nuclear transcription factor Foxp3 as a protein that plays a key role in the biology of Tregs and with GFP as a means of selection, pure populations of Foxp3 expressing cells can be obtained. Among murine CD4+ T cells that express Foxp3, there is a continuum of CD25 expression from negative (or very dim) to very bright. Our analyses of peripheral Foxp3+CD4+CD25dim/- cells suggest that while their transcription of many cytokine, chemokine and receptor genes are similar to Foxp3+CD4+CD25bright T cells, they do not have identical phenotypic and functional properties, with the latter capable of a greater degree of suppression and an enhanced transcription of Interleukin-7. Parenteral administration of a heterologous type II collagen to induce tolerance in a TcR tg mouse model of Collagen-Induced Arthritis increases the percentage of Foxp3+CD4+CD25bright T cells and protects the mice from disease. Adoptive transfer of a Foxp3+cells from CII-tolerized mice confers a greater degree of protection when compared with transfer of equivalent numbers of Tregs from naïve mice.