Cell surface CD28 levels define four CD4+ T cell subsets: abnormal expression in rheumatoid arthritis

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.