Phenotypic characterization of CD4+ T cells that exhibit a transendothelial migratory capacity.
The phenotype of CD4+ T cells capable of transendothelial migration was determined using an in vitro model system, in which cells migrate through a monolayer of endothelial cells (EC) on collagen gels. A specific subset of resting CD4+ memory T cells was found to migrate. T cells within this subset can be defined by the bright expression of CD11a, CD26, CD44, and CD49d. Additionally, the migratory CD4+ T cell population is largely CD58bright, CD31-, CD62L-, and is also enriched in cells that brightly express CD49c, CD49e, and CD49f. Only a minority of the cells are activated, as indicated by expression of CD69. The EC were found to play a central role in facilitating migration of this subset because selective enrichment of CD11abright, CD26bright, CD44bright, CD4+ T cells was not observed when cells migrated in the absence of EC. Activation of the T cells induced a modest degree of migration of an additional subset of CD45RA+, CD31+ naive T cells. In contrast, TNF-alpha activation of the EC increased the transendothelial migration of an additional subset of activated memory T cells that expressed CD69 and CD62L. Neither activation of the T cells, stimulation of the EC, nor the presence of macrophage inflammatory protein-1 alpha (MIP-1 alpha) or RANTES, however, altered the phenotype of the majority of the migratory CD4+ T cell population, which is characteristic of a particular stage of memory cell differentiation. These results suggest that CD4+ T cells acquire the capacity for transendothelial migration at a specific phase of maturation that is only minimally altered by the activation of either the T cell or the EC, or by the presence of specific chemokines in the subendothelial matrix.
Brezinschek
R I
RI
Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, Dallas 75235.
Lipsky
P E
PE
Galea
P
P
Vita
R
R
Oppenheimer-Marks
N
N
D015703:Antigens, CD / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D016207:Cytokines / Q000502:physiology; D004730:Endothelium, Vascular / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D008222:Lymphokines / Q000502:physiology; D019402:Macrophage Inflammatory Proteins; D015846:Monokines / Q000502:physiology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015703:Antigens, CD; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D016207:Cytokines; D008222:Lymphokines; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D014409:Tumor Necrosis Factor-alpha; D015240:Phorbol 12,13-Dibutyrate