A role for LFA‐1 in delaying T‐lymphocyte egress from lymph nodes. (26th February 2013) - Reichardt, Peter
Abstract Lymphocytes use the integrin leukocyte function‐associated antigen‐1 (LFA‐1) to cross the vasculature into lymph nodes (LNs), but it has been uncertain whether their migration within LN is also LFA‐1 dependent. We show that LFA‐1 mediates prolonged LN residence as LFA‐1−/− CD4 T cells have significantly decreased dwell times compared with LFA‐1+/+ T cells, a distinction lost in hosts lacking the major LFA‐1 ligand ICAM‐1. Intra‐vital two‐photon microscopy revealed that LFA‐1+/+ and LFA‐1−/− T cells reacted differently when probing the ICAM‐1‐expressing lymphatic network. While LFA‐1+/+ T cells returned to the LN parenchyma with greater frequency, LFA‐1−/− T cells egressed promptly. This difference in exit behaviour was a feature of egress through all assessed lymphatic exit sites. We show that use of LFA‐1 as an adhesion receptor amplifies the number of T cells returning to the LN parenchyma that can lead to increased effectiveness of T‐cell response to antigen. Thus, we identify a novel function for LFA‐1 in guiding T cells at the critical point of LN egress when they either exit or return into the LN for further interactions.