Imbalanced expression of functional surface molecules in regulatory and effector T cells in systemic lupus erythematosus

Regulatory T (TREG) cells play an important role in maintaining immune tolerance and avoiding autoimmunity. We analyzed the expression of membrane molecules in TREG and effector T cells in systemic lupus erythematosus (SLE). TREG and effector T cells were analyzed for the expression of CTLA-4, PD1, CD28, CD95, GITR, HLA-DR, OX40, CD40L, and CD45RO in 26 patients with active disease, 31 with inactive disease, and 26 healthy controls. TREG cells were defined as CD25(+/high)CD127(Ø/low)FoxP3(+), and effector T cells were defined as CD25(+)CD127(+)FoxP3(Ø). The ratio of TREG to effector T cells expressing GITR, PD1, HLA-DR, OX40, CD40L, and CD45RO was determined in the three groups. The frequency of TREG cells was similar in patients with SLE and controls. However, SLE patients had a decreased frequency of CTLA-4(+)TREG and CD28(+)TREG cells and an increased frequency of CD40L(+)TREG cells. There was a decrease in the TREG/effector-T ratio for GITR(+), HLA-DR(+), OX40(+), and CD45RO(+) cells, and an increased ratio of TREG/effector-T CD40L(+) cells in patients with SLE. In addition, CD40L(+)TREG cell frequency correlated with the SLE disease activity index (P=0.0163). In conclusion, our findings showed several abnormalities in the expression of functionally critical surface molecules in TREG and effector T cells in SLE that may be relevant to the pathogenesis of this disease.