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α 4 β 1 ‐Integrin Activation Is Necessary for High‐Efficiency T‐Cell Subset Interactions with VCAM‐1 under Flow
Author(s) -
LIM YAWCHYN,
WAKELIN MATTHEW W.,
HENAULT LORI,
GOETZ DOUGLAS J.,
YEDNOCK TED,
CABAÑAS CARLOS,
SANCHEZMADRID FRANCISCO,
LICHTMAN ANDREW H.,
LUSCINSKAS FRANCIS W.
Publication year - 2000
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/j.1549-8719.2000.tb00121.x
Subject(s) - epitope , integrin , microbiology and biotechnology , t cell , monoclonal antibody , vcam 1 , cell adhesion , biology , naive t cell , effector , chemistry , cell adhesion molecule , cell , antigen , immunology , antibody , icam 1 , biochemistry , immune system , t cell receptor
Objective : The purpose of this study was to examine the relationship between α 4 β 1 ‐integrin state of activation on CD4 + T‐cell subsets and their adhesive interaction to VCAM‐1 under flow. Methods : Human CD4 + memory and naive T‐cells were freshly isolated and effector‐helper T‐cell subsets, Th1 and Th2 cells, were differentiated in vitro from CD4 + naive T‐cells. The expression of activation/ligand induced epitopes on β 1 ‐integrins of each T‐cell subset was assessed using mAb HUTS21 and mAb 15/7. T‐cell subsets attachment and rolling on VCAM‐1 was determined under defined flow conditions and the rates of attachment (k a ), accumulation, and instantaneous rolling velocities were correlated to their β 1 ‐integrin activation epitope expression. Results : A subset of memory T‐cells constitutively express activation/ligand induced epitopes on β 1 ‐integrins recognized by mAb HUTS21 and 15/7, whereas expression levels on naive T‐cells is low or not detectable. Consistent with an activated phenotype, memory T‐cells exhibit significantly higher rates of attachment and accumulation on VCAM‐1 under flow as compared to naive T‐cells. Interestingly, the expression of activation/ligand induced epitopes on β 1 ‐integrins on Th2 cells and the ability of these cells to interact with VCAM‐1 are comparable to memory T‐cells. In contrast, Th1 cells did not interact as efficiently with VCAM‐1, which correlated with lower expression of activation/ligand induced epitopes on these cells. VCAM‐1 interactions are inhibited completely by pretreatment of the T‐cells with blocking mAb to α 4 ‐integrins or β 1 ‐integrins, indicating that α 4 β 1 is the predominant T‐cell integrin involved. Conclusions : Memory T‐cells express constitutively active α 4 β 1 ‐integrins, as compared to naive T‐cells, which mediate high rates of initial attachment and sustained high‐affinity adhesive interactions with VCAM‐1 under flow conditions in vitro . Similarly, in vitro differentiated Th2 cells but not Th1 cells, which also express elevated levels of activated α 4 β 1 ‐integrins, are capable of sustaining high‐affinity adhesive interactions with VCAM‐1. The differences observed in β 1 ‐integrin activation on T‐cell subsets may underlie selective recruitment patterns of T‐cell subsets in vivo . Microcirculation (2000) 7, 201–214 .