Th17 polarized cells from nonobese diabetic mice following mycobacterial adjuvant immunotherapy delay type 1 diabetes.
IL-17-producing T cells are regarded as potential pathogenic T cells in the induction of autoimmune diseases. Previously, we have shown that injection of adjuvants containing Mycobacterium, such as CFA or bacillus Calmette-Guérin, can prevent type 1 diabetes in NOD mice. We injected NOD mice with mycobacterial products s.c. and analyzed the IL-17-producing cells from the draining lymph nodes and spleen by restimulating whole-cell populations or CD4(+) T cells in vitro with or without IL-17-polarizing cytokines. Mice receiving CFA had a concomitant rise in the level of IL-17, IL-22, IL-10, and IFN-gamma in the draining lymph node and spleen. Adoptive transfer of splenocytes from CFA-injected NOD mice polarized with TGF-beta plus IL-6 or IL-23 delayed the development of diabetes in recipient mice. IL-17-producing cells induced by CFA maintained their IL-17-producing ability in the recipient mice. Injection of CFA also changed the cytokine profile of cells in pancreatic tissue by increasing IL-17, IL-10, and IFN-gamma cytokine gene expression. We suggest that the rise in the level of IL-17 after adjuvant therapy in NOD mice has a protective effect on type 1 diabetes development.
Nikoopour
Enayat
E
Department of Microbiology and Immunology, University of Western Ontario, Dental Sciences Building, London, Ontario N6A 5C1, Canada.
Schwartz
Jordan A
JA
Huszarik
Katrina
K
Sandrock
Christian
C
Krougly
Olga
O
Lee-Chan
Edwin
E
Singh
Bhagirath
B
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D019264:Adoptive Transfer; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D005620:Freund's Adjuvant / Q000008:administration & dosage*; D020381:Interleukin-17 / Q000096:biosynthesis*; D008055:Lipids / Q000008:administration & dosage; D008198:Lymph Nodes / Q000276:immunology / Q000637:transplantation; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D015054:Zymosan / Q000008:administration & dosage
D000276:Adjuvants, Immunologic; D016207:Cytokines; D020381:Interleukin-17; D008055:Lipids; C114843:incomplete Freund's adjuvant; D005620:Freund's Adjuvant; D015054:Zymosan