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 C D45RC isoforms in the rat from a high (CD45RC(+)) to a low molecular w eight 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(-)) sire thought to enter lymph nodes almost exclusively via afferent lymphatics whereas T cells in a resting state (CD45RC(+)) migrate across high endothelial venule s (HEV). The present study monitored the rapid recirculation from bloo d to lymph of allotype-marked CD45RC T-cell subsets. Surprisingly, we found that CD45RC CD4 T cells entered the thoracic duct slightly faste r and reached peak numbers 3 hr earlier (18 hr) than did the CD45RC(+) subset. To determine whether the entrance of CD45RC(+) and RC- subset s was restricted to HEV and afferent lymphatics, respectively, recircu lation of CD4 T cells was monitored in mesenteric lymphadenectomized ( MLNx) rats (on healing the intestinal afferent lymphatics are joined d irectly to the thoracic duct), or in recipients that had had the mesen teric lymph node (MLN) acutely (2-3 hr) deafferentized (entry would be restricted to HEV). In these studies CD45RC(-) CD4 T cells entered th e 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.