Your browser version may not work well with NCBI's Web applications. More information here...
1: J Exp Med. 2008 Jul 7;205(7):1535-41. Epub 2008 Jun 23.
Related Articles, Links
Click here to read Click here to read
Comment in:
IL-12- and IL-23-modulated T cells induce distinct types of EAE based on histology, CNS chemokine profile, and response to cytokine inhibition.

Kroenke MA, Carlson TJ, Andjelkovic AV, Segal BM.

Department of Neurology, Holtom-Garrett Program in Neuroimmunology, University of Michigan, Ann Arbor, MI 48109, USA.

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.

Publication Types:
PMID: 18573909 [PubMed - indexed for MEDLINE]

PMCID: PMC2442630 [Available on 01/07/09]