Figure 4

Proliferation and suppression with IL-7 co-stimulation. (A) Proliferation of CD4⁺CD25⁻ effector T cells (left panel) and CD4⁺CD25^highT regulatory cells (Tregs) (right panel) in response to phyto-haemagglutinin (PHA) alone (1 μg/ml, closed symbols) and in the presence of interleukin (IL)-7 (10 ng/ml, open symbols) was measured in eight clinical remission (CR) patients. Dotted arrows indicate changes in proliferative activity. The direct correlation between effector T-cell proliferation and serum IL-7 (rho = 0.952, P <0.0001) was maintained in the presence of co-stimulation with IL-7 (rho = 0.881, P = 0.004). There was a marginal increase in the proliferation of CD4⁺CD25^highTregs in the presence of IL-7 but proliferation responses remained very low. (B) CD4⁺CD25^highTreg and CD4⁺CD25⁻T cells were co-cultured in the presence of PHA (2 μg/ml). Percentage suppression was measured in controls (n = 5, circles), active rheumatoid arthritis (RA) (n = 5, diamonds) and CR (n = 8, triangles). Suppression was significantly reduced in RA (P <0.0001). A direct trend was observed between suppression capabilities and serum IL-7 levels (rho = 0.589, P = 0.006). (C) The suppression assay was repeated in the presence of IL-7 co-stimulation (10 μg/ml) for the eight patients in CR. Dotted arrows indicate changes in suppression activity. Suppression was marginally affected in four patients with low IL-7 serum levels (<10 pg/ml) but reduced to a greater degree in patients with normal serum IL-7 levels.