Background Rheumatoid arthritis (RA) is likely to be driven by activated Th1 cells. In contrast, Th2 cells and their cytokines, in particular IL-4, are rarely found in RA.
Objectives To determine whether memory or naive CD4pos T cells in RA manifest an intrinsic bias for Th1 differentiation.
Methods Th differentiation was assessed in an ex vivo cell culture system in CD4pos, CD45RApos (naive) and CD45RO pos (memory) T cells isolated from the peripheral blood from patients with active, early RA (mean disease duration < 7 months) who had never been treated with disease modifying anti rheumatic drugs or corticosteroids. The phenotype of freshly isolated and effector cells was determined by flow cytometrical analysis of cytoplasmic cytokines.
Results Th2 effectors could be induced from memory T cells in all healthy controls by stimulation with anti-CD28 and IL-4 but in only one third of the RA patients. Priming conditions that were optimal for the differentiation of Th2 effectors from memory T cells, e.g. priming with anti-CD28 and IL-4 in the absence of TCR-ligation, did not result in Th2 differentiation from resting naive T cells in any individual. In contrast to memory T cells, however, Th2 cells could be induced from naive T cells in all healthy donors and in all RA patients by priming with anti-CD3 in the presence of anti-CD28.
Conclusion CD4pos memory T cells from the majority of patients with early RA manifest a deficiency in the capacity to differentiate into Th2 effectors. In contrast, naive T cells are capable of differentiating into Th2 cells with appropriate stimulation suggesting that the bias in Th1 differentiation of most RA patients is acquired during T cell maturation presumably in response to antigenic stimulation.