title: Adoptive transfer of skin-selective autoimmunity induced by Skn alloantigenic disparities.
abstract: Two unlinked genes of the mouse, Skn-1 and Skn-2, each with alterative alleles, specify alternative cell-surface Skn alloantigens expressed only by epidermal and neural cells. C57BL/6 (B6) and A/J (A) strain mice differ at both Skn loci. Thus lethally irradiated B6 mice restored with (B6 x A)F1 hybrid hematopoietic cells [(B6 x A)/B6 chimeras] reject A strain (Skn-incompatible) skin grafts. Our studies were designed primarily to test the inference that (B6 x A)F1 lymphoid cells, after differentiating in B6 recipients, which lack the Skn alloantigens of A strain mice, may make an Skn-related, skin-selective autoimmune response when returned to their native (B6 x A)F1 habitat. Severe cutaneous lesions did, indeed, ensue after spleen cells of (B6 x A)/B6 chimeras were transferred to (B6 x A)F1 recipients, provided that three conditions were met--namely, (i) priming of the (B6 x A)/B6 chimeric donor by grafting and rejection of Skn-incompatible A strain skin grafts, (ii) stimulation of the recipient's skin as from shaving, at which sites the lesions were mainly located, and (iii) pretreatment of the (B6 x A)F1 recipients with cyclophosphamide or sublethal irradiation. Spleen cells of control female chimeras primed by grafting and rejection of H-Y (Skn-compatible) B6 male skin failed to incite the Skn-typical cutaneous lesions in (B6 x A)F1 recipients, indicating that these lesions were Skn-specific and not a nonspecific consequence of incompatible skin grafting per se. Normally compatible A strain skin grafts, but not Skn-compatible B6 skin grafts, were rejected by cyclophosphamide-treated (B6 x A)F1 recipients of (B6 x A)/B6 spleen cells from Skn-primed chimera donors. Treatment of primed chimeras' spleen cells with antiserum to H-2a (A strain) specifically abolished their capacity to adoptively incite the Skn-related autoimmune syndrome, confirming that the immune cells responsible are of (B6 x A)F1 origin and are not residual B6 derivatives. These findings add weight to the status of Skn systems as agents of tissue-selective histoincompatibility and, perhaps, of clinical disorders with a known or suspected autoimmune basis affecting the skin.
authors.affiliation: Department of Microbiology, Marshall University, School of Medicine, Huntington, WV 25755.
authors.forename: S H
authors.initials: SH
authors.lastname: Jackman
authors.forename: E A
authors.initials: EA
authors.lastname: Boyse
authors.forename: E H
authors.initials: EH
authors.lastname: Goldberg
mesh_terms: D000483:Alleles; D000818:Animals; D015551:Autoimmunity; D002678:Chimera; D006084:Graft Rejection; D016219:Immunotherapy, Adoptive; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D012867:Skin / Q000276:immunology* / Q000473:pathology / Q000528:radiation effects; D016038:Skin Transplantation / Q000276:immunology*; D013154:Spleen / Q000276:immunology