Title

IL-7 Is a Critical Factor in Modulating Lesion Development in Skn-Directed Autoimmunity

Document Type

Article

Publication Date

7-1-2006

Abstract

In a murine model of autoimmunity targeted against the epidermal cell Ags, Skn, adoptive transfer of Skn-immune T cells to immunosuppressed recipients elicits skin lesions in areas of mild epidermal trauma. In this study, we examined peripheral regulation of Skn-induced autoreactivity disrupted by rendering the mice immunoincompetent. We found that regulation of Skn-directed autoimmunity was restored by cotransfer of normal syngeneic spleen cells at twice the concentration of Skn-immune cells and was evidenced by significantly reduced lesion severity by days 5–7 post-cotransfer compared with animals given injections of Skn-immune cells alone. Enrichment and depletion of normal CD4 or CD8 spleen cells and RT-PCR analysis of selected cytokines identified CD4 cells as the regulatory cells in the cotransfer inoculum; however, significant reduction in lesion severity was observed only when there was a concomitant increase in levels of IL-7. The role of IL-7 was further supported in that mice cotransferred with Skn-immune cells plus normal spleen cells, but also treated with anti-IL-7 Ab, no longer exhibited reduced lesion severity. To determine whether IL-7 expression without normal spleen cell cotransfer could modulate lesion development, an IL-7-encoding plasmid (pCMV-Tag1-IL-7) was topically delivered to sites flanking the stressed skin site in Skn-induced autoimmune mice. Daily application of 15g of pCMV-Tag1-IL-7 significantly suppressed lesion severity. Our results support a mechanism for CD4 T cells and IL-7 in contributing to the control of autoreactivity.

Comments

This article is available as an open access article from The American Association of Immunologists, Inc. Permission to link to the article has been granted. Final version can be found at http://www.jimmunol.org/content/176/7/3978.full.pdf+html

Copyright © 2006 by The American Association of Immunologists All rights reserved.