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 of highly differentiated T lymphocytes that accumulate in vivo within the affected joints of patients with rheumatoid arthritis (RA). Although it is known that CD45RO(+) T lymphocytes migrate to sites of inflammation in vivo, it is not clear whether within this subset the CD45RB(lo) 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 endothelial cells (HUVEC). These migrating cells were CD45RO(+) and enriched for low CD45RB expression. In addition, both the CD45RO(+)CD45RB(lo) subset and migrating cells expressed increased levels of beta(1) and beta(2) integrins and CD44. The percentage of CD45RO(+)CD45RB(lo) T lymphocytes was increased in the circulation of patients with acute Epstein-Barr virus (EBV) infection. These in vivo activated cells also expressed increased levels beta(1) and beta(2) integrins and CD44, and showed an enhanced rate of transmigration compared with resting T lymphocytes. Transmigration of T lymphocytes was increased using the chemokines 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 selective migration of the CD45RB(lo) subset was maintained. Thus although the rate of T-lymphocyte transmigration could be influenced by a number factors, the CD45RO(+)CD45RB(lo) subset has a migratory advantage suggesting that more differentiated CD45RO(+)CD45RB(lo) T lymphocytes are selectively recruited to sites of inflammation.