Differential expression of VLA-α4 and VLA-β1 discriminates multiple subsets of CD4⁺CD45R0⁺ "memory" T cells

Given the importance of adhesion in T cell development, we have undertaken systematic flow cytometric analysis of CD4 T cells to determine relationships between the developmentally regulated marker CD45R0 and adhesion receptors (five VLA integrin chains). The most important findings are that: 1) expression of α3, α5, and α6 are closely coregulated with β1 on CD4 cells, while regulation of VLA-α4 is quite discordant. 2) CD45R0^- cells, generally understood to be naive cells, have low homogeneous expression of VLA-α3, VLA-α4, VLA-α5, VLA-α6, and β1 integrin chains; studies of cord blood CD4 cells confirm the low homogeneous expression of α4 and β1 on naive cells. 3) In marked contrast, CD45R0⁺ cells, generally understood to be memory cells, show not only an overall increase in expression of these integrins (relative to CD45R0^- cells) but also heterogeneity. Dramatic heterogeneity is revealed when the markers VLA-α4 and β1 are analyzed together. Many CD45R0⁺ cells show increased levels of both VLA-α4 and VLA-β1; however, some have increased levels principally of either VLA-β1 or VLA-α4. We hypothesize that T cells becoming memory cells in different microenvironments specialize their integrin phenotype, thereby acquiring distinctive functional and homing capacities; in this process, VLA-4 (CD49d) appears to play a unique role.