NKT cells in lupus prone NZB/W mice are abnormal and expression of Ly108 (SLAMF6) affects proinflammatory cytokine secretion and help for autoreactive B cells (44.46)

Abstract

Abstract Systemic lupus erythematosus is an autoantibody mediated disease that causes immune complex glomerulonephritis as well as injury to multiple organs. Invariant natural killer T cells (iNKT) from non-autoimmune strains of mice regulate and suppress graft versus host disease, transplantation immunity and autoimmunity. We have shown that iNKT cells from lupus prone NZB/W mice are abnormal and promote rather than suppress spontaneous in vitro immunoglobulin and autoantibody secretion of autoreactive B cells. To determine the role of iNKT cells in the induction and augmentation of immune cell activation, we examined cytokine production of purified iNKT cells from NZB/W and control C57BL/6 mice in vitro. We found that upon stimulation of NKT stimulatory ligand, α-galactosylceramide, young NZB/W splenocytes secreted much higher IFNγ, IL-4 and IL-17 compared with C57BL/6 mice. With activation of CD3 and CD28, sorted NZB/W splenic iNKT cells, but not conventional T cells, also produced dramatically higher IFNγ and IL-4 than controls. Interestingly, we found the expression of Ly108, a SLAM family member (SLAMF6), affected cytokine production, and promoted help for immunoglobulin secretion by autoreactive B cells. Sorted NZB/W Ly108+ iNKT cells produced less IL-17 but more efficiently helped B cells secrete IgG but not IgM as compared to Ly108- iNKT cells. In conclusion, expression of the SLAM family member, Ly108, promoted the interaction of NZB/W iNKT cells with autoreactive B cells.