SELECTIVE MIGRATION OF HIGHLY DIFFERENTIATED PRIMED T-CELLS, DEFINED BY LOW EXPRESSION OF CD45RB, ACROSS HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS - EFFECTS OF VIRAL-INFECTION ON TRANSMIGRATION

Low expression of CD45RB on CD45RO(+) T lymphocytes defines a subset o f highly differentiated T lymphocytes that accumulate in vivo within t he affected joints of patients with rheumatoid arthritis (RA). Althoug h it is known that CD45RO(+) T lymphocytes migrate to sites of inflamm ation in vivo, it is not clear whether within this subset the CD45RB(l o) cells are selectively recruited or develop in situ within the joint . Using a transwell system we show that a small proportion of resting T lymphocytes migrated across unactivated human umbilical vein endothe lial cells (HUVEC). These migrating cells were CD45RO(+) and enriched for low CD45RB expression. In addition, both the CD45RO(+)CD45RB(lo) s ubset and migrating cells expressed increased levels of beta(1) and be ta(2) integrins and CD44. The percentage of CD45RO(+)CD45RB(lo) T lymp hocytes was increased in the circulation of patients with acute Epstei n-Barr virus (EBV) infection. These in vivo activated cells also expre ssed increased levels beta(1) and beta(2) integrins and CD44, and show ed an enhanced rate of transmigration compared with resting T lymphocy tes. Transmigration of T lymphocytes was increased using the chemokine s RANTES and lymphotactin and the cytokine interleukin-15 (IL-15). In addition, infection of the HUVEC with cytomegalovirus (CMV) led to an enhanced movement of T lymphocytes. In all of these cases the selectiv e migration of the CD45RB(lo) subset was maintained. Thus although the rate of T-lymphocyte transmigration could be influenced by a number f actors, the CD45RO(+)CD45RB(lo) subset has a migratory advantage sugge sting that more differentiated CD45RO(+)CD45RB(lo) T lymphocytes are s electively recruited to sites of inflammation.