Adjuvant immunotherapy is dependent on inducible nitric oxide synthase

被引:41
作者
Kahn, DA
Archer, DC
Gold, DP
Kelly, CJ
机构
[1] Univ Calif San Diego, Biomed Sci Grad Program, La Jolla, CA 92161 USA
[2] Univ Calif San Diego, Dept Med, La Jolla, CA 92161 USA
[3] Dept Vet Affairs, San Diego Healthcare Syst, San Diego, CA 92161 USA
[4] Sidney Kimmel Canc Ctr, San Diego, CA 92121 USA
关键词
experimental allergic encephalomyelitis; Freund's adjuvant; immunosuppression; interleukin; 6; tumor necrosis factor alpha;
D O I
10.1084/jem.193.11.1261
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Rodents immunized with complete Freund's adjuvant (CFA) are resistant to subsequent attempts to induce autoimmune disease, while animals immunized with incomplete Freund's adjuvant (IFA) remain susceptible. Mycobacterial extracts can stimulate inducible nitric oxide synthase (NOS2) gene transcription. Robust expression of NOS2 has been linked to suppression of T cell proliferation and alterations in immune responses. Our studies investigated the hypothesis that the immunoprotective effect of CFA before immunization requires functional NOS2. NOS2 gene expression is chronically elevated in lymph nodes and spleens of CFA-immunized mice. Maximal expression of NOS2 after CFA immunization requires the presence of functional type I tumor necrosis factor a receptor (TNFR1) and interferon gamma. Groups of nontreated and CFA-preimmunized male C57BL/6J or C57BL/6NOS2(-/-) mice were immunized with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 in CFA to induce experimental allergic encephalomyelitis (EAE). Wild-type C57BL/6J mice were protected fi-om the development of symptoms of EAE, while the NOS2(-/-) mice failed to be protected. NOS2-dependent effects of CFA included an augmentation of the MOG-specific IgG1 response, a decrease in interleukin 6 production by MOG-reactive lymphocytes, and a marked decrease in mononuclear cell infiltrates in the central nervous system. These studies support the hypothesis that CFA immunization modulates immune responses through a nitric oxide-dependent mechanism.
引用
收藏
页码:1261 / 1267
页数:7
相关论文
共 37 条
[1]   NEUROLOGIC DISEASE INDUCED IN TRANSGENIC MICE BY CEREBRAL OVEREXPRESSION OF INTERLEUKIN-6 [J].
CAMPBELL, IL ;
ABRAHAM, CR ;
MASLIAH, E ;
KEMPER, P ;
INGLIS, JD ;
OLDSTONE, MBA ;
MUCKE, L .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (21) :10061-10065
[2]   MACROPHAGES REGULATE INDUCTION OF DELAYED-TYPE HYPERSENSITIVITY AND EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS IN SJL MICE [J].
CUA, DJ ;
HINTON, DR ;
KIRKMAN, L ;
STOHLMAN, SA .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1995, 25 (08) :2318-2324
[3]  
Eugster HP, 1998, EUR J IMMUNOL, V28, P2178, DOI 10.1002/(SICI)1521-4141(199807)28:07<2178::AID-IMMU2178>3.0.CO
[4]  
2-D
[5]  
FALK GA, 1969, J IMMUNOL, V103, P1248
[6]  
Fenyk-Melody JE, 1998, J IMMUNOL, V160, P2940
[7]  
Gabbai FB, 1997, J IMMUNOL, V159, P6266
[8]   Nitric oxide and the immunomodulation of experimental allergic encephalomyelitis [J].
Gold, DP ;
Schroder, K ;
Powell, HC ;
Kelly, CJ .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1997, 27 (11) :2863-2869
[9]   UNRESPONSIVENESS TO EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS IN LEWIS RATS PRETREATED WITH COMPLETE FREUNDS-ADJUVANT [J].
HEMPEL, K ;
FREITAG, A ;
FREITAG, B ;
ENDRES, B ;
MAI, B ;
LIEBALDT, G .
INTERNATIONAL ARCHIVES OF ALLERGY AND APPLIED IMMUNOLOGY, 1985, 76 (03) :193-199
[10]   Absence of functional inducible NO synthase enhances the efficacy of tolerance induced by high dose antigen feeding [J].
Kahn, DA ;
Archer, DC ;
Kelly, CJ .
JOURNAL OF IMMUNOLOGY, 2000, 165 (11) :6116-6122