Increased interleukin-4 production by NK T cells in systemic lupus erythematosus

It has been reported that production of interleukin (IL)-4, a T helper (Th)-2-type cytokine, might play an important role in the pathogenesis of systemic lupus erythematosus (SLE). On the other hand, it is known that NK1.1(+) cells which belong to CD4, CD8 double-negative, or CD4(+) cells are associated with initial IL-4 production and Th2 differentiation in mice although human equivalent cells are unknown. In order to study the profile of IL-4-producing cells in SLE, cytoplasmic IL-4 and various surface antigens on peripheral mononuclear cells were analyzed. Peripheral mononuclear cells were stimulated for 5 h by phorbol ester and ionomycin in the presence of monensin, fixed, and permeabilized with paraformaldehyde and saponin solution. Then cytoplasmic IL-4 and various surface antigens were analyzed by flow cytometry. IL-4-producing cells in SLE were phenotypically the same as those which produce IL-4 normally and frequently bore activated T-cell (CD7, CD25, CD28, CD29) and NK-cell markers (CD56, CD57). Double-negative T cells and CD57(+) T cells were increased in number and were more frequently positive for cytoplasmic IL-4 in SLE compared with normal controls and various infectious diseases. It was suggested that T cells with NK cell markers, CD57(+) T cells, which are known to extrathymically differentiate, might be involved in the pathogenesis of SLE as a counterpart of mouse NK1.1(+) cells.