Expression of the α1β1 integrin, VLA-1, marks a distinct subset of human CD4+ memory T cells
Itamar Goldstein, … , Hong Jiang, Leonard Chess
Itamar Goldstein, … , Hong Jiang, Leonard Chess
Published November 1, 2003
Citation Information: J Clin Invest. 2003;112(9):1444-1454. https://doi.org/10.1172/JCI19607.
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Expression of the α1β1 integrin, VLA-1, marks a distinct subset of human CD4+ memory T cells

Abstract

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-4hi 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.

Authors

Itamar Goldstein, Shomron Ben-Horin, Jianfeng Li, Ilan Bank, Hong Jiang, Leonard Chess

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VLA-1 is expressed only in a subset of the activated CD45RO+ CD4+ T cell...
VLA-1 is expressed only in a subset of the activated CD45RO+ CD4+ T cells. (a) CD4+ T cells were isolated from PBLs as described in Methods. Subsequently, the cells were stimulated with irradiated APCs and TSST-1 (upper four panels) or anti-CD3 (bottom panel). The cultures were assayed at day 8 for the cell surface coexpression of CD4 and Vβ2, together with VLA-1, CD45RO, CD25, or VLA-2. The data shown are representative of at least ten independent experiments in different normal donors. (b) CD4+ PBLs were stimulated twice (every 10 days) with APCs and TSST-1. Subsequently, the cultures were purified into VLA-1– or VLA-1+ cell fractions. The cells were maintained in recombinant human IL-2–containing medium and stimulated every 10 days. The two cultures were analyzed for surface expression of VLA-1, both at day 1 and 8 weeks later. The data are representative of more than five independent experiments in different normal blood donors.