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 15 mug 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.
Department of Microbiology, Immunology, and Molecular Genetics, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25704, USA.
Pamela J
PJ
Staton
A Betts
AB
Carpenter
Susan H
SH
Jackman
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology*; D015551:Autoimmunity / Q000276:immunology*; D015704:CD4 Antigens / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D015316:Genetic Therapy; D015851:Interleukin-7 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000276:immunology / Q000378:metabolism; D012867:Skin / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000378:metabolism
D015704:CD4 Antigens; D015851:Interleukin-7; D012333:RNA, Messenger; D020395:Receptors, Interleukin-7