This diminished capacity of cytokine production is characteristic for exhausted CD8+ T cells, and can be a result of prolonged antigen exposure followed by T-cell hyporesponsiveness.4 Further analyses of CD8+ T cells, using specific markers for exhaustion, are required to formally test whether these CD8+ T cells are indeed exhausted during the earliest phases of RA. This evidence concerns the gene CD8A and rheumatoid arthritis.