Expression of the alpha1beta1 integrin, VLA-1, marks a distinct subset of human CD4+ memory T cells

J Clin Invest. 2003 Nov;112(9):1444-54. doi: 10.1172/JCI19607.

Abstract

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 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Autoimmune Diseases / etiology
  • Bacterial Toxins*
  • Biomarkers
  • CD4-Positive T-Lymphocytes / chemistry*
  • CD4-Positive T-Lymphocytes / immunology
  • Enterotoxins / pharmacology
  • Humans
  • Immunologic Memory*
  • Immunophenotyping
  • Integrin alpha1beta1 / analysis*
  • L-Selectin / analysis
  • Leukocyte Common Antigens / analysis
  • Receptors, Antigen, T-Cell / physiology
  • Receptors, CCR7
  • Receptors, Chemokine / analysis
  • Receptors, Chemokine / physiology
  • Superantigens*
  • Tetanus Toxoid / pharmacology
  • Th1 Cells / immunology

Substances

  • Bacterial Toxins
  • Biomarkers
  • CCR7 protein, human
  • Enterotoxins
  • Integrin alpha1beta1
  • Receptors, Antigen, T-Cell
  • Receptors, CCR7
  • Receptors, Chemokine
  • Superantigens
  • Tetanus Toxoid
  • enterotoxin F, Staphylococcal
  • L-Selectin
  • Leukocyte Common Antigens