Adjuvant treatment suppresses IL-17 production by T cell-independent myeloid sources in nonobese diabetic mice.

Recent studies have shown that Th17 cells, as a distinct lineage from Th1 and Th2 subsets, play an obligatory role in the pathogenesis of autoimmune diseases. It is well known that immunotherapy with Complete Freund's adjuvant (CFA) is effective in preventing from the onset of autoimmune diabetes in nonobese diabetic (NOD) mice. In the present study, we investigated whether CFA treatment restrained Th17 development and down-regulated Th17-related cytokine production in NOD mice. Th17-related cytokines (i.e. IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-6, TGF-beta) production in splenocytes was decreased dramatically on day 18 following CFA immunization. This effect was also observed at 10 and 20 week after adjuvant treatment. Injection of IL-17 into CFA-treated diabetes-free mice led to occurrence of overt diabetes, indicating that therapeutic effects of adjuvant treatment may be partially due to suppressing Th17 commitment. Interestingly, the main producer of IL-17 resided in a population of myeloid cells, which negatively expressed makers of neutrophil or macrophages. IL-23 stimulation did not alter the distribution of IL-17 in myeloid cells. Furthermore, this pattern of IL-17 expression was also present in Balb/c and C57BL/6 strains. These findings may have important implications for understanding of mechanisms underlying adjuvant treatment on autoimmune diseases.

Gao X ，Ding G ，Wang Z ，Fu H ，Ni Z ，Ma J ，Song S ，Liu F ，Fu Z ... -  《-》

Th17 polarized cells from nonobese diabetic mice following mycobacterial adjuvant immunotherapy delay type 1 diabetes.

Nikoopour E ，Schwartz JA ，Huszarik K ，Sandrock C ，Krougly O ，Lee-Chan E ，Singh B ... -  《-》

Upregulating CD4+CD25+FOXP3+ regulatory T cells in pancreatic lymph nodes in diabetic NOD mice by adjuvant immunotherapy.

Tian B ，Hao J ，Zhang Y ，Tian L ，Yi H ，O'Brien TD ，Sutherland DE ，Hering BJ ，Guo Z ... -  《-》

Endogenous immune response to glutamic acid decarboxylase (GAD67) in NOD mice is modulated by adjuvant immunotherapy.

We have shown that immunization of non-obese diabetic (NOD) mice with adjuvants (CFA or BCG) prevents the onset of diabetes by induction of regulatory cells. Since autoimmune responses to glutamic acid decarboxylase (GAD) are up-regulated in insulin-dependent diabetes mellitus (IDDM), in this study GAD67-specific antibody, T cell proliferation and lymphokine production patterns were analysed in the adjuvant-treated mice to characterize the regulatory mechanisms underlying the protection. We used both spontaneous diabetes and syngeneic islet transplantation models in NOD mice. Protection against spontaneous diabetes and prevention of syngeneic islet graft rejection by CFA or BCG treatment was found to be accompanied by the production of long lasting and high titre anti-GAD67 antibody of IgG1 isotype in the sera. Upon in vitro stimulation with GAD67, draining lymph node and spleen cells from CFA-immunized NOD mice or syngeneic islet-grafted and BCG-protected NOD mice produced much more IL-4, whereas there was no significant change in IFN-gamma production. The strong early T cell proliferative response to GAD67 in CFA or BCG-immunized NOD mice was followed by a low or unresponsiveness state. Taken together, these results suggest a shift in Th1/Th2 balance in the GAD67-specific endogenous immune response to a change in Th2 levels after adjuvant treatment. We postulate that the protective effect of CFA or BCG is due to the diversion of GAD-specific endogenous cellular immune response to a non-pathogenic humoral response.

Qin HY ，Elliott JF ，Lakey JR ，Rajotte RV ，Singh B ... -  《JOURNAL OF AUTOIMMUNITY》

Adjuvant immunotherapy increases beta cell regenerative factor Reg2 in the pancreas of diabetic mice.

Huszarik K ，Wright B ，Keller C ，Nikoopour E ，Krougly O ，Lee-Chan E ，Qin HY ，Cameron MJ ，Gurr WK ，Hill DJ ，Sherwin RS ，Kelvin DJ ，Singh B ... -  《-》