Regulatory T-cell compartmentalization and trafficking

Abstract

CD4(+)CD25(+)FOXP3(+) regulatory T cells (CD4(+) Treg cells) are thought to differentiate in the thymus and immigrate from the thymus to the periphery. Treg cells can regulate both acquired and innate immunity through multiple modes of suppression. The cross-talk between Treg cells and targeted cells, such as antigen-presenting cells (APCs) and T cells, is crucial for ensuring suppression by Treg cells in the appropriate microenvironment. Emerging evidence suggests that Treg compartmentalization and trafficking may be tissue or/and organ specific and that distinct chemokine receptor and integrin expression may contribute to selective retention and trafficking of Treg cells at sites where regulation is required. In this review, the cellular and molecular signals that control specialized migration and retention of Treg cells are discussed.

Figure 1.

Organ/tissue trafficking and distribution of Treg cells. Distinct chemokine receptors and integrin molecules implicated in Treg-cell organ/tissue trafficking and compartmentalization. Bone marrow–derived CXCL12 mediates Treg-cell bone marrow trafficking. Environmental CCL22 mediates Treg-cell trafficking into human ovarian cancer and mouse cardiac grafts. The lymphoid homing molecules CCR7 and CD62L may facilitate lymphoid homing of Treg cells. Certain CC chemokines and integrins may mediate Treg-cell trafficking into inflammatory tissues/organs.