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IL-7 Is a Critical Factor in Modulating Lesion Development in Skn-Directed Autoimmunity¹

Pamela J. Staton^*, A. Betts Carpenter and Susan H. Jackman^2,*

^* Departments of Microbiology, Immunology, and Molecular Genetics and Department of Pathology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25704

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 15 µg 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.