title: Transfer of CD8(+) cells induces localized hair loss whereas CD4(+)/CD25(-) cells promote systemic alopecia areata and CD4(+)/CD25(+) cells blockade disease onset in the C3H/HeJ mouse model.
abstract: Alopecia areata (AA) is a suspected hair follicle specific autoimmune disease. The potential for cell transfer of AA using the C3H/HeJ mouse model was examined. Cells isolated from lymph nodes and spleens of AA-affected mice using magnetic bead conjugated monoclonal antibodies were subcutaneously injected into normal C3H/HeJ recipients. Within 5 wk, all CD8(+) cell-injected mice exhibited localized hair loss exclusively at the site of injection that persisted until necropsy. In contrast, some CD4(+) and CD4(+)/CD25(-) cell-injected mice developed extensive, systemic AA, and a combination of CD8(+) and CD4(+)/CD25(-) cells injected yielded the highest frequency of systemic AA induction. CD4(+)/CD25(+) cells were less able to transfer the disease phenotype, partially blockaded systemic AA induction by CD4(+)/CD25(-) cells, and prevented CD8(+) cell-induced, injection site-localized hair loss. CD11c(+) and CD19(+) cells failed to promote significant phenotype changes. Increases in co-stimulatory ligands CD40 and CD80, plus increased leukocyte apoptosis resistance with reduced CD95, CD95L, and CD120b expression, were associated with successful alopecia induction. The results suggest that CD8(+) cells may be the primary instigators of the hair loss phenotype. However, systemic disease expression fate is, apparently determined by CD4(+)/CD25(-) cells, while CD4(+)/CD25(+) lymphocytes may play a predominantly regulatory role.
authors.affiliation: Division of Dermatology, University of British Columbia, Vancouver, BC, Canada. kevin@keratin.com
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: McElwee
authors.forename: Pia
authors.initials: P
authors.lastname: Freyschmidt-Paul
authors.forename: Rolf
authors.initials: R
authors.lastname: Hoffmann
authors.forename: Sabine
authors.initials: S
authors.lastname: Kissling
authors.forename: Susanne
authors.initials: S
authors.lastname: Hummel
authors.forename: Mario
authors.initials: M
authors.lastname: Vitacolonna
authors.forename: Margot
authors.initials: M
authors.lastname: Zöller
mesh_terms: D019264:Adoptive Transfer; D000506:Alopecia Areata / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D000818:Animals; D018941:Antigens, CD19 / Q000032:analysis; D017209:Apoptosis; D039521:CD11c Antigen / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D018960:Hyaluronan Receptors / Q000032:analysis; D051379:Mice; D008809:Mice, Inbred C3H; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D012867:Skin / Q000473:pathology
chemical_list: D018941:Antigens, CD19; D039521:CD11c Antigen; D018960:Hyaluronan Receptors; D015375:Receptors, Interleukin-2