title: Autoimmune vitiligo does not require the ongoing priming of naive CD8 T cells for disease progression or associated protection against melanoma.
abstract: Vitiligo is a CD8 T cell-mediated autoimmune disease that has been shown to promote the longevity of memory T cell responses to melanoma. However, mechanisms whereby melanocyte/melanoma Ag-specific T cell responses are perpetuated in the context of vitiligo are not well understood. These studies investigate the possible phenomenon of naive T cell priming in hosts with melanoma-initiated, self-perpetuating, autoimmune vitiligo. Using naive pmel (gp10025-33-specific) transgenic CD8 T cells, we demonstrate that autoimmune melanocyte destruction induces naive T cell proliferation in skin-draining lymph nodes, in an Ag-dependent fashion. These pmel T cells upregulate expression of CD44, P-selectin ligand, and granzyme B. However, they do not downregulate CD62L, nor do they acquire the ability to produce IFN-γ, indicating a lack of functional priming. Accordingly, adult thymectomized mice exhibit no reduction in the severity or kinetics of depigmentation or long-lived protection against melanoma, indicating that the continual priming of naive T cells is not required for vitiligo or its associated antitumor immunity. Despite this, depletion of CD4 T cells during the course of vitiligo rescues the priming of naive pmel T cells that are capable of producing IFN-γ and persisting as memory, suggesting an ongoing and dominant mechanism of suppression by regulatory T cells. This work reveals the complex regulation of self-reactive CD8 T cells in vitiligo and demonstrates the overall poorly immunogenic nature of this autoimmune disease setting.
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755.
authors.forename: Katelyn T
authors.initials: KT
authors.lastname: Byrne
authors.forename: Peisheng
authors.initials: P
authors.lastname: Zhang
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Turk
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D053804:Granzymes / Q000096:biosynthesis; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000378:metabolism; D007156:Immunologic Memory / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D019041:L-Selectin / Q000096:biosynthesis / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008544:Melanocytes / Q000276:immunology; D008545:Melanoma / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000096:biosynthesis / Q000378:metabolism; D012867:Skin / Q000276:immunology; D015854:Up-Regulation; D014820:Vitiligo / Q000276:immunology*; D058951:gp100 Melanoma Antigen / Q000235:genetics / Q000378:metabolism
chemical_list: D018960:Hyaluronan Receptors; D019007:P-Selectin; D058951:gp100 Melanoma Antigen; D019041:L-Selectin; D007371:Interferon-gamma; D053804:Granzymes; C509214:Gzmb protein, mouse