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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Depleting VLA-1+ cells from the PBLs significantly abrogates the prolife...
Depleting VLA-1+ cells from the PBLs significantly abrogates the proliferative response to TT. (a and b) CD4+ T cells from fresh PBLs of normal individuals were depleted of the VLA-1+ cells or sham depleted (see Methods). Subsequently, the two cell groups were labeled with CFSE and stimulated with either TT or TSST-1 and irradiated APCs. The cells were harvested at day 8 and analyzed for CFSE dilution. (a) A representative experiment for donor 6. (b) The bar graph shows the results from seven different individuals. The P value of 0.02 (Wilcoxon signed rank test) was obtained by comparing the relative reduction induced by VLA-1 depletion in the combined TT-stimulation experiments to the relative reduction measured in the TSST-stimulation experiments (asterisk indicates percentage of reduction in the TT response when comparing sham to VLA-1 depletion). (c and d) The sham-depleted CD4+ PBLs or the VLA-1– fraction with a increasing numbers of VLA-1+ cells added back (0%, 1%, 5%, and 25%) were stimulated with TT and cultured for 8 days and then assayed for cellular divisions and VLA-1 expression. (c) A representative experiment in one donor. (d) Graph shows the combined results obtained from five different individuals. The proliferation index was calculated as the percentage of proliferation in a given sample divided by the percentage of proliferation in the pure VLA-1– sample. The error bars represent ± SEM, and the P value was less than 0.01 (repeated measures ANOVA test).