Chemoattractant receptors and lymphocyte egress from extralymphoid tissues: changing requirements during the course of inflammation (94.21)

Abstract

Memory/effector T cells traffic efficiently through extralymphoid tissues entering from the blood and leaving via the afferent lymph. During inflammation, T cell traffic through the affected tissue dramatically increases, however, dynamics and mechanisms of T cell exit from inflamed tissues are poorly characterized. Here we show that, unexpectedly, large numbers of lymphocytes including T cells capable of producing IFN-γ and IL-17 leave the chronically inflamed skin, showing that memory/effector T cells also egress sites of inflammation. Whereas efficient egress from acutely inflamed skin required lymphocyte-expressed CCR7, chronic inflammation promoted CCR7-independent exit. CCR7-independent exit at late time points of inflammation was sensitive to pertussis toxin implying the contribution of alternative chemoattractant receptors. Our data suggest that CCR7 is an important receptor for lymphocyte egress from both resting and inflamed tissues, but that alternative exit receptors come into play during chronic inflammation allowing the egress of CCR7- as well as CCR7+ lymphocytes.