The Journal of Experimental Medicine
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Published online June 23, 2008
doi:10.1084/jem.20080159
The Journal of Experimental Medicine, Vol. 205, No. 7, 1535-1541
The Rockefeller University Press, 0022-1007 $30.00
© 2008 Kroenke et al.
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BRIEF DEFINITIVE REPORT

 IL-12– and IL-23–modulated T cells induce distinct types of EAE based on histology, CNS chemokine profile, and response to cytokine inhibition

Mark A. Kroenke1,3, Thaddeus J. Carlson3, Anuska V. Andjelkovic2, and Benjamin M. Segal1

1 Holtom-Garrett Program in Neuroimmunology, Department of Neurology, University of Michigan, and 2 Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109
3 Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642

CORRESPONDENCE Benjamin M. Segal: bmsegal{at}umich.edu

The interleukin (IL)-12p40 family of cytokines plays a critical role in the development of experimental autoimmune encephalomyelitis (EAE). However, the relative contributions of IL-12 and IL-23 to the pathogenic process remain to be elucidated. Here, we show that activation of uncommitted myelin-reactive T cells in the presence of either IL-12p70 or IL-23 confers encephalogenicity. Adoptive transfer of either IL-12p70– or IL-23–polarized T cells into naive syngeneic hosts resulted in an ascending paralysis that was clinically indistinguishable between the two groups. However, histological and reverse transcription–polymerase chain reaction analysis of central nervous system (CNS) tissues revealed distinct histopathological features and immune profiles. IL-12p70–driven disease was characterized by macrophage-rich infiltrates and prominent NOS2 up-regulation, whereas neutrophils and granulocyte–colony-stimulating factor (CSF) were prominent in IL-23–driven lesions. The monocyte-attracting chemokines CXCL9, 10, and 11 were preferentially expressed in the CNS of mice injected with IL-12p70–modulated T cells, whereas the neutrophil-attracting chemokines CXCL1 and CXCL2 were up-regulated in the CNS of mice given IL-23–modulated T cells. Treatment with anti–IL-17 or anti–granulocyte/macrophage-CSF inhibited EAE induced by transfer of IL-23–polarized, but not IL-12p70–polarized, cells. These findings indicate that autoimmunity can be mediated by distinct effector populations that use disparate immunological pathways to achieve a similar clinical outcome.

© 2008 Kroenke et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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