CD99 facilitates rearrangement of actin cytoskeleton during T cell activation.

Abstract

Abstract CD99 is an O-glycosylated transmembrane protein expressed on most hematopoietic cells and has been known to play roles in transendothelial migration of leukocytes. Several reports showed that blocking CD99 on T cells rendered the cells unable to infiltrate into inflamed tissue sites. To understand how CD99 affects T cell migration, we examined the dynamics of antigen-specific T cells in the presence or absence of CD99 during allo-response. When we adoptively transferred WT or CD99-deficient T cell into B6 mice followed by intraperitoneal immunization of splenocytes from allogeneic mice, CD99-deficient antigen-specific T cells were rarely detected in the peritoneum, the antigen-existing target site, relative to WT T cells on day 3 post-immunization, consistent with previous studies. Unexpectedly, however, CD99-deficient antigen-specific T cells were detected in the peritoneum with comparable numbers to WT antigen-specific T cells at later time point, day 7. This delayed migration in CD99-deficient T cells was caused by slower activation than CD99-sufficient T cells in the spleen. We also found that actin dynamics and microcluster movement were impaired in CD99-deficient T cells during synapse formation, and these defects were due to insufficient Rac1 activation in the absence of CD99. Thus, these results demonstrate that CD99 is an important mediator of actin cytoskeleton rearrangement for adequate T cell activation and migration.