To examine the correlation between CD28 expression and clonal proliferation, we have analyzed the T cell receptor (TCR) diversity of CD4+ CD28- T cells in normal individuals and in RA patients.
In this study, we screened for polymorphisms of human CD28, CD80 and CD86 genes, and detected that polymorphisms were tested for the association with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).
Thus, the capacity for increased production of cytokines IFN-gamma and TNF-alpha in the aged individual by the dominant CD8+ CD28- subset may have a profound influence on the clinical state by aggravating inflammatory pathologies such as rheumatoid arthritis, and possibly Alzheimer's disease and Crohn's disease.
They showed a twofold increase in mean CD28 expression (P < 0.05), whereas each of the CD28(+) subsets in the inactive RA patients showed reduced expression when compared to healthy donors.
Inasmuch as rheumatoid arthritis and aging are also associated with elevated levels of TNF-alpha, we examined whether this proinflammatory cytokine influences CD28 expression.
CD4(+)CD28(null) T cell clones isolated from RA patients with vasculitis were found to express killer cell immunoglobulin-like receptors (KIRs) with the stimulatory KIR2DS2 often present in the absence of opposing inhibitory receptors with related specificities.
Killer Ig-like receptors (KIRs) are expressed on CD4(+)CD28(null) T cells, a highly oligoclonal subset of T cells that is expanded in patients with rheumatoid arthritis.
We found that peripheral blood CD4+ T cells from patients with active rheumatoid arthritis (RA) were able to produce greater amounts of interferon gamma after CD3 and CD28 costimulation in the presence of 1 ng/ml IL-10 than were normal control CD4+ T cells, although their surface expression of the type 1 IL-10 receptor was increased.
Peripheral blood mononuclear cells (PBMC) from patients with RA (n = 24) were separated, then stimulated with various agents including anti-CD3, anti-CD28, phytohemagglutinin (PHA) and several inflammatory cytokines and chemokines.
Magnetically sorted CD4+,CD25- and CD4+,CD25+ T cells derived from the PB and SF obtained from RA patients were stimulated alone or in coculture with anti-CD3 monoclonal antibody (mAb) and autologous antigen-presenting cells, in the absence or presence of anti-CD28 mAb or the proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), or IL-7.
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.
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.
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.