IL-7 Is a Critical Factor in Modulating Lesion Development in Skn-Directed Autoimmunity
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.
Staton PJ, Carpenter AB, Jackman SH. IL-7 is a critical factor in modulating lesion development in Skn-directed autoimmunity. J Immunol 2006;176:3978-3986.