Expression of the α1β1 integrin, VLA-1, marks a distinct subset of human CD4+ memory T cells

The α1β1 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 CD45RO⁺/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.