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 CD45RBlo 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+CD45RBlo subset and migrating cells expressed increased levels of beta 1 and beta 2 integrins and CD44. The percentage of CD45RO+CD45RBlo 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 CD45RBlo subset was maintained. Thus although the rate of T-lymphocyte transmigration could be influenced by a number factors, the CD45RO+CD45RBlo subset has a migratory advantage suggesting that more differentiated CD45RO+CD45RBlo T lymphocytes are selectively recruited to sites of inflammation.
Borthwick
N J
NJ
Department of Clinical Immunology, Royal Free Hospital School of Medicine, London, UK.
Akbar
A N
AN
MacCormac
L P
LP
Lowdell
M
M
Craigen
J L
JL
Hassan
I
I
Grundy
J E
JE
Salmon
M
M
Yong
K L
KL
D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D018925:Chemokines / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology; D004730:Endothelium, Vascular / Q000276:immunology*; D006566:Herpesviridae Infections / Q000276:immunology; D004854:Herpesvirus 4, Human; D006801:Humans; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014412:Tumor Virus Infections / Q000276:immunology; D014471:Umbilical Veins / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology*
D018925:Chemokines; D016207:Cytokines; D017493:Leukocyte Common Antigens