HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Pastor, S. Articles by Ward, E. S. Search for Related Content PubMed PubMed Citation Articles by Pastor, S. Articles by Ward, E. S.

Autoantigen Immunization at Different Sites Reveals a Role for Anti-Inflammatory Effects of IFN- in Regulating Susceptibility to Experimental Autoimmune Encephalomyelitis¹

Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390

Experimental autoimmune encephalomyelitis is induced in B10.PL (H-2^u) mice by immunization with the immunodominant N-terminal epitope of myelin basic protein, Ac1-9. In the present study, we show that the site of immunization impacts disease incidence and severity. This effect is more marked in female mice than in males. Although immunization in the flanks is effective in eliciting disease, delivery of Ag in the footpad and tailbase results in poor induction. Analyses of the immune responses in female mice following different immunization regimens indicates that resistance to disease is accompanied by higher levels of IFN- and CD11b⁺Gr-1^int myeloid cells. Such myeloid cells are known to have a suppressive function, and consistent with this knowledge, blockade of IFN- results in increased disease activity and decreased levels of splenic CD11b⁺Gr-1^int cells. Conversely, injection of adjuvants (CFA or Pam₃CSK₄) in the footpad decreases experimental autoimmune encephalomyelitis incidence and severity. Our study indicates that the site of immunization can impact the magnitude of the ensuing inflammatory response, and that at a certain threshold a protective, regulatory circuit can be elicited.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Grant R01 AI/NS 42949 from the National Institutes of Health and Grant RG 2411 from the National Multiple Sclerosis Society. A.M. was supported by a Fellowship BAE 00/5030 and 01/5037 from the Fondo de Investigacion Sanitaria. CIBEREHD is funded by the Instituto de Salud Carlos III.

² S.P. and A.M. contributed equally to this work.

³ Current address: Ophthalmology Institute of Alicante (Vissum Corporation), Avda. Denia s/n, Edificio Vissum, Alicante, Spain.

⁴ Current address: Immunology Service, University Hospital "Virgen de la Arrixaca", El Palmar, Murcia, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD o Ciberehd), Spain.

⁵ Address correspondence and reprint requests to Dr. E. Sally Ward, Department of Immunology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-9093. E-mail address: sally.ward{at}utsouthwestern.edu

⁶ Abbreviations used in this paper: EAE, experimental autoimmune encephalomyelitis; MBP, myelin basic protein; LN, lymph node.