Dysregulation of T Helper Cell Cytokines in Autoimmune Prone NZB x NZW Fl Mice

Multifactorial involvement in the pathogenesis of autoimmune NZB/W F1 mice has been well documented. To further elucidate the role of cytokines in the disease development of murine lupus, single spleen cells isolated from NZB/W Fl and non-autoimmune C57BL/6 mice were stimulated with T cell mitogens or anti-CD3 antibody at pre-determined optimal concentration. Supernatants were collected and assayed for production of cytokines including IL-2, γ-IFN, IL-3, IL-4, IL-5 and IL-10. In both young and old mice, cytokine profiles by mitogen-stimulated T cells showed higher TH2 (type 2 T helper) cell-related cytokine production in NZB/W Fl mice compared to those in non-autoimmune C57BL/6 mice. In contrast, cytokines produced by TH1 (type 1 T helper) cells, such as γ-IFN and IL-2, were lower in NZB/W F1 mice by stimulation with either mitogen or anti-CD3 antibody. In addition, cytokine production at different time points also demonstrated decreased γ-IFN and increased IL-4 levels by anti-CD3 stimulated splenic cells in autoimmune NZB/W F1 mice. Furthermore, the IL-10 levels produced by lipopolysaccharide (LPS)-stimulated splenic and peritoneal exudate cells were higher in young NZB/W Fl mice compared to those in C57BL/6 mice. Our data suggest that dysregulation between TH1 and TH2 cells may play an important role in the pathogenesis of autoimmunity in NZB/W F1 mice.