Differential expression of VLA-alpha 4 and VLA-beta 1 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 alpha 3, alpha 5, and alpha 6 are closely coregulated with beta 1 on CD4 cells, while regulation of VLA-alpha 4 is quite discordant. 2) CD45R0- cells, generally understood to be naive cells, have low homogeneous expression of VLA-alpha 3, VLA-alpha 4, VLA-alpha 5, VLA-alpha 6, and beta 1 integrin chains; studies of cord blood CD4 cells confirm the low homogeneous expression of alpha 4 and beta 1 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-alpha 4 and beta 1 are analyzed together. Many CD45R0+ cells show increased levels of both VLA-alpha 4 and VLA-beta 1; however, some have increased levels principally of either VLA-beta 1 or VLA-alpha 4. 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.