T cell egress via the afferent lymph modulates the course of local tissue inflammation (CAM1P.149)

Abstract

Abstract T cells recirculate through extralymphoid tissues by entering from the blood and egressing via the afferent lymph. While T cell migration into effector sites is key to inflammation, the influence of T cell egress in this process is not known. In a mouse model, antigen recognition at the effector site reduced the egress of antigen-specific pro-inflammatory Th1 cells. Transgenic expression of ‘tissue exit receptor’ CCR7 enhanced egress of antigen-sequestered Th1 cells from the inflamed site and ameliorated inflammation. In contrast, lack of CCR7 on Th1 cells diminished their tissue egress while enhancing inflammation. Lymph-borne Th1 and Th17 cells draining the inflamed skin of sheep chemotaxed to the CCR7 ligand CCL21, suggesting the CCR7-CCL21 axis as a physiological target in regulating inflammation. In conclusion, exit receptors can be targeted to modulate T cell dwell time and inflammation at effector sites, revealing T cell tissue egress via lymph as a novel parameter of the pathophysiology of inflammation.