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Cell surface CD28 levels define four CD4+ T cell subsets: abnormal expression in rheumatoid arthritis.
L I Salazar-Fontana1, E Sanz, I Mérida
1Laboratory of Immunology and Oncology, School of Medicine, University of Alcalá-Centro de Investigaciones Biológicas (CSIC) Associated Unit, Ctra. Madrid-Barcelona Km. 33, 28871 Alcalá de Henares, Madrid, Spain.
Clinical Immunology (Orlando, Fla.)
|April 25, 2001
Summary
Rheumatoid arthritis patients exhibit altered CD28 T cell expression, with higher CD28(high) cells and impaired T cell proliferation. This CD28 dysregulation correlates with disease activity, suggesting a role in immune balance.
Area of Science:
- Immunology
- Rheumatology
- Cell Biology
Background:
- CD28 is a crucial costimulatory receptor on CD4(+) T cells, regulating immune responses.
- In vivo regulation of CD28 expression is less understood compared to in vitro studies.
- Rheumatoid arthritis (RA) involves complex immune dysregulation, potentially affecting T cell phenotypes.
Purpose of the Study:
- To investigate CD28 and CD152 expression and function in rheumatoid arthritis (RA) patients.
- To compare T cell phenotypes between active RA, inactive RA, and healthy donors.
- To explore the relationship between CD28 expression, T cell function, and RA disease activity.
Main Methods:
- Three-color flow cytometry was used to define CD4(+) T cell subsets based on CD28 expression levels (CD28(-), CD28(low), CD28(int), CD28(high)).
- Expression of CD28, CD152, and CD80 was analyzed in peripheral blood of 33 RA patients and 24 healthy donors.
- In vitro T cell activation assays were performed using anti-CD3 and anti-CD28 antibodies to assess proliferation and upregulation.
Main Results:
- RA patients (active and inactive) displayed increased CD4(+)CD28(high) and decreased CD4(+)CD28(low) T cells compared to healthy donors.
- CD4(+)CD28(high) T cells from RA patients showed an in vivo activated phenotype (CD45RO(+), CD5(high), IL-2Ralpha(+)).
- Active RA patients had higher mean CD28 expression, while inactive RA patients showed reduced CD28 expression on subsets and hypoproliferative responses, normalized by CD28 crosslinking.
Conclusions:
- In vivo CD28 expression is significantly disregulated in rheumatoid arthritis patients, correlating with disease activity.
- Altered CD28 expression impacts T cell activation and proliferation, contributing to immune dysregulation in RA.
- Modulation of CD28 surface levels may represent a therapeutic target for balancing immune responsiveness and tolerance in RA.