Lymphocyte Trafficking: CD4 T Cells with a 'memory' Phenotype (CD45RC-) Freely Cross Lymph Node High Endothelial Venules in Vivo

Antigen encounter not only induces a change in surface expression of CD45RC isoforms in the rat from a high (CD45RC+) to a low molecular weight molecule (CD45RC-), but also stimulates changes in expression of adhesion molecules that regulate CD4 T-cell migration. T cells with an activated or 'memory' phenotype (CD45RC-) are thought to enter lymph nodes almost exclusively via afferent lymphatics whereas T cells in a resting state (CD45RC+) migrate across high endothelial venules (HEV). The present study monitored the rapid recirculation from blood to lymph of allotype-marked CD45RC T-cell subsets. Surprisingly, we found that CD45RC- CD4 T cells entered the thoracic duct slightly faster and reached peak numbers 3 hr earlier (18 hr) than did the CD45RC+ subset. To determine whether the entrance of CD45RC+ and RC- subsets was restricted to HEV and afferent lymphatics, respectively, recirculation of CD4 T cells was monitored in mesenteric lymphadenectomized (MLNx) rats (on healing the intestinal afferent lymphatics are joined directly to the thoracic duct), or in recipients that had had the mesenteric lymph node (MLN) acutely (2-3 hr) deafferentized (entry would be restricted to HEV). In these studies CD45RC- CD4 T cells entered the MLN across HEV on an equal basis with T cells expressing a CD45RC+ phenotype. Contrary to currently held dogma the results showed that, in vivo, CD4 T cells with a memory phenotype freely enter lymph nodes (LN) across HEV as well as via afferent lymphatics.