Migration and function of FoxP3+ regulatory T cells in the hematolymphoid system.

FoxP3+ T cells play critical roles in regulation of the hematolymphoid system and prevention of autoimmunity. Many FoxP3+ T cells, generated in thymus as the result of T cell receptor (TCR) recognition of self antigens, preferentially migrate to secondary lymphoid tissues such as lymph nodes and spleen in a manner similar to conventional naïve T cells. FoxP3+ T cells differentiated in the periphery acquire homing phenotype to bone marrow and nonlymphoid tissues. Consistently, lymphoid- and nonlymphoid-tissue-homing FoxP3+ T cell subsets express different trafficking and chemokine receptors. FoxP3+ T cells regulate hematopoiesis by limiting the activation of immune cells and their production of hematopoietic cytokines available for stem and progenitor cells. In mice deficient in FoxP3+ T cells, aberrant regulation of hematopoiesis including excessive myelopoiesis occurs. In transplantation of allogenic hematopoietic cells, FoxP3+ T cells selectively suppress harmful graft-vs-host disease (GVHD) but leave beneficial graft-vs-leukemia (GVL) activity intact. Therefore, FoxP3+ T cells play essential roles in regulation of the hematolymphoid system in health and diseases, and are likely to be utilized as effective therapeutics for many diseases in the hematolymphoid system in the future.