Expression of the alpha1beta1 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 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.
Department of Medicine, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, PH8E Suite 101, New York, New York 10032, USA. lc19@columbia.edu
Itamar
I
Goldstein
Shomron
S
Ben-Horin
Jianfeng
J
Li
Ilan
I
Bank
Hong
H
Jiang
Leonard
L
Chess
D001327:Autoimmune Diseases / Q000209:etiology; D001427:Bacterial Toxins; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry* / Q000276:immunology; D004768:Enterotoxins / Q000494:pharmacology; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D039222:Integrin alpha1beta1 / Q000032:analysis*; D019041:L-Selectin / Q000032:analysis; D017493:Leukocyte Common Antigens / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000032:analysis / Q000502:physiology; D018089:Superantigens; D013745:Tetanus Toxoid / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology
D001427:Bacterial Toxins; D015415:Biomarkers; C515370:CCR7 protein, human; D004768:Enterotoxins; D039222:Integrin alpha1beta1; D011948:Receptors, Antigen, T-Cell; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D018089:Superantigens; D013745:Tetanus Toxoid; C030107:enterotoxin F, Staphylococcal; D019041:L-Selectin; D017493:Leukocyte Common Antigens