Expression of CD39 by Human Peripheral Blood CD4+CD25+ T Cells Denotes a Regulatory Memory Phenotype

• Published in: American journal of transplantation Vol. 10; no. 11; pp. 2410 - 2420
• Main Authors: Dwyer, K. M., Hanidziar, D., Putheti, P., Hill, P. A., Pommey, S., McRae, J. L., Winterhalter, A., Doherty, G., Deaglio, S., Koulmanda, M., Gao, W., Robson, S. C., Strom, T. B.
• Format: Journal Article
• Language: English
• Published: Malden, USA Blackwell Publishing Inc 01-11-2010; Wiley
• Subjects: Adenosine; Allografts; Antigens, CD - biosynthesis; Apyrase - biosynthesis; Biological and medical sciences; CD25 antigen; CD4 antigen; CD4 Antigens - immunology; CD4 regulatory cells; CD4-Positive T-Lymphocytes - immunology; CD73 antigen; Ectonucleotidase; Foxp3 protein; Graft rejection; Graft Rejection - immunology; Humans; Immunologic Memory; Immunoregulation; Immunosuppressive agents; Inflammation; Interferon-gamma - biosynthesis; Interleukin 17; Interleukin-17 - biosynthesis; Interleukin-2 Receptor alpha Subunit - immunology; Kidney; Kidney diseases; Kidney Failure, Chronic - immunology; Kidney Transplantation; Lymphocytes T; Medical sciences; Memory cells; Peripheral blood; Phenotype; Pyrophosphatases - biosynthesis; Pyrophosphatases - immunology; regulatory T cells; renal allograft; renal allograft rejection; Surface markers; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; T-Lymphocyte Subsets - immunology; T-Lymphocytes, Regulatory - immunology; Th17 Cells - immunology; Human; Graft(material); CD4 T lymphocyte; Immune response; Memory; renal allograft; Transplantation; Gene expression; Homotransplantation; Kidney; Rejection; regulatory T cells; Blood cell; Phenotype; Regulation(control); Treatment; Urinary system; renal allograft rejection; Surgery; T-Lymphocyte; CD4 regulatory cells; Graft; Regulatory cell
• ISSN: 1600-6135; 1600-6143
• DOI: 10.1111/j.1600-6143.2010.03291.x

We have shown that CD39 and CD73 are coexpressed on the surface of murine CD4+Foxp3+ regulatory T cells (Treg) and generate extracellular adenosine, contributing to Treg immunosuppressive activity. We now describe that CD39, independently of CD73, is expressed by a subset of blood‐derived human CD4+CD25+CD127lo Treg, defined by robust expression of Foxp3. A further distinct population of CD4+CD39+ T lymphocytes can be identified, which do not express CD25 and FoxP3 and exhibit the memory effector cellular phenotype. Differential expression of CD25 and CD39 on circulating CD4+ T cells distinguishes between Treg and pathogenic cellular populations that secrete proinflammatory cytokines such as IFNγ and IL‐17. These latter cell populations are increased, with a concomitant decrease in the CD4+CD25+CD39+ Tregs, in the peripheral blood of patients with renal allograft rejection. We conclude that the ectonucleotidase CD39 is a useful and dynamic lymphocytes surface marker that can be used to identify different peripheral blood T cell‐populations to allow tracking of these in health and disease, as in renal allograft rejection.
CD39 in conjunction with CD4 and CD25 defines four T cell populations that are dynamic and can be tracked in states of inflammation.