Abatacept is a biologic agent selectively targeting the T-cell costimulatory signal delivered through the CD80/86-CD28 pathway and was approved in December 2005 by the US Food and Drug Administration and in May 2007 by European Medicines Agency for the treatment of patients with rheumatoid arthritis in combination with methotrexate.
The expansion of CD4(+)CD28(null) cells in RA patients was associated with TNFA genotype, even at diagnosis, and linked to markers of aggressive disease in patient carriers of the minor allele.
Killer cell immunoglobulin-like receptors (KIR) expressed on surface of natural killer cells and CD28 null T-cells which are present in synovial membrane of RA.
Forty-four patients with RA, displaying a distinct CD4(+) CD28(null) T cell population in blood, were recruited for this study; the methylation status of the IFNG locus was examined in isolated T cell subsets, and intracellular cytokine production (IFN-γ, TNF, IL-17) and chemokine receptor expression (CXCR3, CCR6 and CCR7) were assessed by flow cytometry on T cells from the two compartments.
In addition, The percentage of peripheral CD4+DR3+T cells of RA was significantly higher than that of healthy controls (HC), and this increased percentage of CD4+DR3+T cells was obviously up-regulated when stimulated with anti-CD3 and anti-CD28 antibody in RA patients.
The CD28 gene is similarly down-regulated in CD4(+) lymphocytes from both healthy elderly people and patients with rheumatoid arthritis (RA) because of impaired protein-binding activity of the 'α' sequence in its promoter region.
The gene includes the CD28 IVS3 +17T/C polymorphism that could be associated with susceptibility to RA whereas the soluble concentrations of CD28 (sCD28) could be related to clinical activity.
A senescent CD4(+)CD28(-) T cell subset develops with aging and in chronic inflammatory diseases like rheumatoid arthritis, and is implicated in plaque rupture and myocardial infarctions.
Fibroblast-like synoviocytes (FLS) and T cells can activate each other in vitro, and in vivo interactions between these cells may be important in rheumatoid arthritis (RA), yet FLS lack significant expression of CD28 ligands.