IL-22 production of effector CD4⁺ T-cells is altered in SLE patients

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by T-cell-dependent B-cell activation and altered T-cell response. Co-stimulatory and co-inhibitory molecules regulate and exert T-cell differentiation, survival and cytokine production. CD134⁺ and PD-1⁺ T-cells in SLE patients are increased in SLE. The aim of this study was to characterize CD134⁺ and PD-1⁺CD4⁺ T-cells according to their ability to produce IFN-γ, IL-21 and IL-22 in SLE patients.

Peripheral blood of 39 SLE patients and 19 healthy controls (HC) was stimulated with phorbol myristate acetate (PMA) calcium ionophore (Ca-Io). The expression of IFN-γ, IL-21 and IL-22 T-cells within the CD134⁺ and PD-1⁺ T-cells was analyzed by flow cytometry. Disease activity was assessed by SLE Disease Activity Index.

Peripheral unstimulated CD134⁺ and PD-1⁺ CD4⁺ T-cells were significantly increased in patients with lupus nephritis. Upon stimulation both, CD134⁺ and PD-1⁺ CD4⁺ T-cells, produced significantly less IFN-γ in SLE patients as compared to HC. The percentages of IL-22 within the CD134⁺CD4⁺ T-cells were also significantly decreased in SLE as compared to HC.

CD134⁺ and PD-1⁺CD4⁺ T-cells have mainly a Th1 effector T-cell signature. A lower proportion produces also IL-21 and IL-22. The impaired capacity to produce IFN-γ and IL-22 in SLE patients may contribute to the pathogenesis of the disease.