Dysregulated lymphocyte proliferation and differentiation in patients with rheumatoid arthritis

• Published in: Blood Vol. 100; no. 13; pp. 4550 - 4556
• Main Authors: Ponchel, Frederique, Morgan, Ann W., Bingham, Sarah J., Quinn, Mark, Buch, Maya, Verburg, Robert J., Henwood, Judy, Douglas, Susan H., Masurel, Aurelie, Conaghan, Philip, Gesinde, Moji, Taylor, Julia, Markham, Alexander F., Emery, Paul, van Laar, Jacob M., Isaacs, John D.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.12.2002; The Americain Society of Hematology
• Subjects: Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Arthritis, Rheumatoid - immunology; Biological and medical sciences; Bone marrow, stem cells transplantation. Graft versus host reaction; C-Reactive Protein - analysis; Cell Differentiation - drug effects; Cell Division - drug effects; Cell Lineage; Diseases of the osteoarticular system; Female; Humans; Immune Tolerance; Immunologic Memory; Immunophenotyping; Inflammation - immunology; Inflammatory joint diseases; Lymphocyte Activation - drug effects; Lymphocyte Count; Male; Medical sciences; Models, Immunological; Phytohemagglutinins - pharmacology; Receptors, Antigen, T-Cell - analysis; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - pathology; Thymus Gland - pathology; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Human; Cell proliferation; Immunopathology; Chronic; Pathophysiology; Rheumatoid arthritis; Diseases of the osteoarticular system; Autoimmune disease; Inflammatory joint disease; Cellular immunity; Cell differentiation
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2002-03-0671

Rheumatoid arthritis (RA) is a chronic, inflammatory disease of the synovium of uncertain pathogenesis. A number of phenotypic and functional T-cell defects have been described in RA, including abnormal clonal expansions and suppressed proliferative responses, which suggest a defect in T-cell differentiation. Here, we show that RA patients possess fewer naive CD4+ T cells than healthy controls. Furthermore, a smaller proportion of these cells contains a T-cell receptor excision circle (TREC). Patients with RA also have unusual populations of T cells. These include immature cells characterized as CD45RBbrightCD45RA+CD62L− by flow cytometry and a large population that coexpresses CD45RA and CD45RO. These cells are hyperresponsive to mitogen and TCR stimulation when compared to naive cells. Additionally, an unusual putative central memory subset expressing CD62L, but not CD45RA, appears in RA patients at the expense of more typical cells. Levels of C-reactive protein correlate inversely with the TREC content of naive T cells and positively with the sizes of naive and immature atypical T-cell subsets. These data suggest that inflammation drives proliferation of naive T cells in RA and encourages their differentiation into atypical, hyperresponsive progeny. TREC content of individual naive and atypical T-cell subsets suggests an ontogeny consistent with this hypothesis. These studies provide further evidence of a T-cell differentiation defect in RA, which could explain some of the well-characterized immunologic features of the disease.