Expression of the alpha 1 beta 1 integrin, VLA-1, marks a distinct subset of human CD4(+) memory T cells

The alpha1beta1 integrin, very late antigen-1 (VLA-1), is a collagen receptor expressed in many CD4(+)T cells localizing to inflamed tissues. Here we show that the expression of VLA-1 is a stable marker of a distinct subset of CD4(+) memory T cells. Thus, in human peripheral blood lymphocytes (PBLs), approximately 1-4% of the CD4(+)T cells express VLA-1, and following T cell receptor activation ex vivo, the percentage of VLA-1(+) cells increases within the CD45RO(+) population. Importantly, the activated VLA-1(+) and VLA-1(-) cells can be isolated and maintained in culture as phenotypically stable subsets. Functionally, CD4(+) memory T cells, operationally defined as the cells that divide rapidly following stimulation with a recall antigen, are highly enriched for VLA-1(+) cells. Moreover, depletion of the small fraction of VLA-1(+) cells present in CD4(+) PBLs prior to stimulation significantly abrogated the proliferative response to recall antigens. Notably, the VLA-1(+) cells in fresh CD4(+) PBLs are composed of resting CD4SRO(+)/RA(-), CCR7(-), CD62L(+), CD25(-), and VLA-4(hi) cells. Interestingly, this VLA-1(+) subset is enriched for Th1-type cells, and Th1-polarizing conditions during T cell activation favor the emergence of VLA-1(+) cells. Thus, VLA-1 expression is a stable marker of a unique subset of human memory CD4(+)T cells that predominantly differentiates into Th1 cells.