Brief Report: Deficient Thymic Output in Rheumatoid Arthritis Despite Abundance of Prethymic Progenitors

OBJECTIVE: To determine the frequencies of common lymphoid progenitors (CLPs) and recent thymic emigrants (RTEs) in patients with rheumatoid arthritis (RA) and healthy control subjects. METHODS: Flow cytometry was performed to determine the frequencies of CLPs and RTEs in the peripheral blood of 101 control subjects and 51 patients with RA. Thirteen of these patients were also analyzed longitudinally for 6 months after initiation of treatment with a tumor necrosis factor (TNF) inhibitor. RESULTS: A significant correlation between the frequencies of CLPs and RTEs was observed in healthy control subjects. The frequencies of both CLPs and RTEs decreased with age and correlated inversely with absolute lymphocyte numbers in peripheral blood. In patients with RA, the frequencies of RTEs were significantly decreased compared with the frequencies in control subjects. Importantly, the frequencies of CLPs were significantly higher in patients with RA compared with control subjects. Therapeutic TNF blockade further increased the frequency of CLPs, thereby normalizing thymic output, as indicated by an increase in the number of RTEs. CONCLUSION: Thymic insufficiency in RA is not attributable to an inadequate supply of progenitor cells to the thymus. Thus, insufficient numbers of RTEs could result from inadequate thymic T cell neogenesis, or alternatively, could be a consequence of high CD4+ T cell turnover, homeostatic proliferation, and subsequent dilution of the RTE population.