Cd4+ cd28- T lymphocytes in rheumatoid arthritis (ra)

Patients with RA frequently carry clonally expanded CD4 T lymphocytes which carry the CD28- cell surface phenotype. CD4+ CD28- cells are an infrequent finding in normal individuals. To determine whether the CD4+ CD28- T cell compartment is expanded in RA patients and whether the expansion correlates with the clinical presentation of RA, we evaluated 106 RA patients and 36 age-matched controls by FACS analysis. The percent of CD4+ CD28- T cells was significantly higher in RA patients versus controls (2.5 vs 1.1%, p=0.04). In the RA as well as the normal population, the size distribution of the CD4+ CD28- compartment was bimodal. Thirty percent of all RA patients versus 54% of all normal controls had no, or a very low, number of CD4+ CD28- T cells. In 70% of the RA population, the compartment of CD4+ CD28- cells was expanded, in some patients as high as 45%. The major clinical variable which correlated with an expanded CD4+ CD28- T cell subset was the presence of extra-articular disease. Patients with rheumatoid vasculitis had a median of 17.6% CD4+ CD28- T cells compared to 1.5% for RA patients without extra-articular manifestations (p=0.005). Patients with nodular disease had a median of 6.9% (p=0.008). Large expansions of the CD4+ CD28- compartment were generally not seen in individuals younger than 45 years. In contrast, disease duration and HLA-DR polymorphism were not independent risk factors. Our data suggest that CD4+ CD28- T cells are important in the extra-articular manifestations of RA and are consistent with the model that the expansion of the CD4+ CD28- compartment is a risk factor for, rather than a consequence of, severe disease.