DYSREGULATION OF T-HELPER CELL CYTOKINES IN AUTOIMMUNE-PRONE NZB X NZW F1-MICE

Multifactorial involvement in the pathogenesis of autoimmune NZB/W F1 mice has been well documented. To further elucidate the role of cytoki nes in the disease development of murine lupus, single spleen cells is olated from NZB/W F1 and non-autoimmune C57BL/6 mice were stimulated w ith T cell mitogens or anti-CD3 antibody at pre-determined optimal con centration. Supernatants were collected and assayed for production of cytokines including IL-2, gamma-IFN, IL-3, IL-4, IL-5 and IL-10. In bo th 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 F1 mice compared to those in non-autoimmune C57BL/6 mice. In contrast, cytokines produced by TH1 (type 1 T helper) cells, such as g amma-IFN and IL-2, were lower in NZB/W F1 mice by stimulation with eit her mitogen or anti-CD3 antibody. In addition, cytokine production at different time points also demonstrated decreased gamma-IFN and increa sed IL-4 levels by anti-CD3 stimulated splenic cells in autoimmune NZB /W F1 mice. Furthermore, the IL-10 levels produced by lipopolysacchari de (LPS)-stimulated splenic and peritoneal exudate cells were higher i n young NZB/W F1 mice compared to those in C57BL/6 mice. Our data sugg est that dysregulation between TH1 and TH2 cells may play an important role in the pathogenesis of autoimmunity in NZB/W F1 mice.