Objective: The purpose of this study was to examine the relationship between α₄β₁‐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 β¹‐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 β₁‐integrin activation epitope expression.

Results: A subset of memory T‐cells constitutively express activation/ligand induced epitopes on β₁‐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 β₁‐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 α₄‐integrins or β₁‐integrins, indicating that α₄β₁ is the predominant T‐cell integrin involved.

Conclusions: Memory T‐cells express constitutively active α₄β₁‐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 α₄β₁‐integrins, are capable of sustaining high‐affinity adhesive interactions with VCAM‐1. The differences observed in β₁‐integrin activation on T‐cell subsets may underlie selective recruitment patterns of T‐cell subsets in vivo. Microcirculation (2000) 7, 201–214.