The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 4 June 2001.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 165K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kahn, D. A.
Right arrow Articles by Kelly, C. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kahn, D. A.
Right arrow Articles by Kelly, C. J.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© The Rockefeller University Press, 0022-1007/2001/6/1261/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 11, June 4, 2001 1261-1268

Original Article

Adjuvant Immunotherapy Is Dependent on Inducible Nitric Oxide Synthase

Daniel A. Kahna, D. Clay Archerb, Daniel P. Goldc, and Carolyn J. Kellya,b,d
a Biomedical Sciences Graduate Program, University of California at San Diego, San Diego, California 92093
b Department of Medicine, University of California at San Diego, San Diego, California 92093
c Sidney Kimmel Cancer Center, San Diego, California 92121
d Department of Veterans Affairs, San Diego Healthcare System, San Diego, California 92161

Correspondence to: Carolyn J. Kelly, UCSD and VASDHS, 111-H, 3350 La Jolla Village Dr., San Diego, CA 92161. Tel:858-552-8585 ext. 2522 Fax:858-642-6243 E-mail:ckelly{at}ucsd.edu.

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 {alpha} 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 from 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.

Key Words: experimental allergic encephalomyelitis, Freund's adjuvant, immunosuppression, interleukin 6, tumor necrosis factor {alpha}


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS