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.
Goldstein
Itamar
I
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
Ben-Horin
Shomron
S
Li
Jianfeng
J
Bank
Ilan
I
Jiang
Hong
H
Chess
Leonard
L
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