Green fluorescent protein (GFP)-expressing wild-type, and nontransgenic mouse vibrissa follicle cells were cultured and implanted to mouse ears and footpads. Dermal papiller (DP)-derived cells and cells from the peribulbar dermal sheath "cup" (DSC) induced new hair follicles in both implanted ears and footpads, while nonbulbar dermal sheath cells did not. Confocal microscopy revealed that GFP-expressing DP and DSC cells induced hair growth associated with the formation of DP exclusively comprised of fluorescent cells. In mouse ears, but not footpads, fluorescent DP and DSC cells could also be identified in DP along with nonfluorescent cells. DSC cells were characterized in vivo and in vitro by low alkaline phosphatase activity in contrast to high alkaline phosphatase in DP cells. The results indicate transplanted DP and DSC cells were equally capable of DP formation and hair follicle induction. This suggests the DP and peribulbar DSC may be functionally similar. In addition to observing papillae exclusively composed of GFP-expressing cells, DP and DSC cells may also have combined with resident cells to form papillae composed of implanted GFP-expressing cells and host-derived non-GFP-expressing cells. Alkaline phosphatase expression may be utilized as a simple marker to identify hair follicle mesenchyme derived cells with hair follicle inductive abilities.

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Pemphigus vulgaris (PV) is an autoimmune disease caused by immunoglobulin G (IgG) autoantibodies against the desmosomal adhesion molecules, desmoglein (Dsg)3 and Dsg1. The aim of the study was to relate IgG reactivity of 123 PV sera and 40 control sera against NH(2)-terminal non-conformational epitopes of Dsg3 and Dsg1 with disease activity and clinical phenotype by enzyme-linked immunosorbent assay. The results show that (i) the overall reactivity and the titres of IgG reactive with the Dsg3 ectodomain, Dsg3(1-566), significantly correlated with the disease activity of the PV patients; (ii) IgG reactivity against the NH(2)-terminus of Dsg3, Dsg3(1-161), was associated with active PV while there was no direct correlation between the IgG titres and the disease activity; (iii) IgG reactivity against the NH(2)-terminus of Dsg3, Dsg3(1-161), was associated with mucosal and mucocutaneous PV; (iv) IgG titres against a small stretch of the NH(2)-terminus of Dsg3, Dsg3(25-88), were associated with active PV; and (v) IgG in the PV sera detected non-conformational epitopes in addition to the previously identified conformation-dependent epitopes of the Dsg3 and Dsg1 ectodomains.

Pemphigus vulgaris (PV) is associated with autoantibodies against desmoglein (Dsg) 3 inducing epidermal loss of adhesion. The major pathogenic epitopes of Dsg3 are presumably dependent of their conformation. The aim of this study was to characterize the IgG reactivity of sera from a cohort of clinically well-characterized PV patients against presumably non-conformational subdomains of the Dsg3 ectodomain including recently described NH 2 -terminal immunodominant epitopes. By ELISA, IgG reactivity against distinct subdomains of Dsg3 was related to disease activity and the clinical phenotype of PV patients. Our findings suggest that (i) autoantibody from PV sera react with non-conformational epitopes of Dsg3; (ii) IgG reactivity against the NH 2 -terminus and the extracellular domains (EC) 2-4 of Dsg3 was associated with active PV, while IgG titres were not strictly correlated with disease activity and (iii) IgG reactivity against the EC1-4 was associated with mucosal dominant PV and was decreased in cutaneous dominant PV. The findings may help to define more refined serological disease markers of PV.

Grafting alopecia areata affected C3H/HeJ mouse skin to littermates induces alopecia areata, but high dietary soy oil reduces alopecia areata susceptibility. Alopecia areata affected and resistant mice were characterized to evaluate possible mechanisms involved in alopecia areata resistance. Of 44 mice that received alopecia areata affected skin grafts but failed to develop alopecia areata, only two of 22 receiving further alopecia areata affected skin grafts developed alopecia areata, whereas 39 of 44 controls developed alopecia areata. Alopecia areata affected skin contained increased numbers of CD4+ and CD8+ cells, increases in pro inflammatory T helper 1 and T helper 2 type cytokines, and upregulation of CD28, CD40L, and their ligands. In draining lymph nodes, a relatively high number of antigen-presenting cells was recovered, whereas several CD44v variants were downregulated. In contrast, alopecia areata resistant mouse skin did not display increased numbers of CD4+ and CD8+ cells, whereas counter-regulatory cytokines interleukins 4 and 10 were upregulated. High expression of CD28, CD80, CD86, CD40, CTLA4, CD44v variants, and FasL occurred in alopecia areata resistant mouse spleens. In vitro, lymph node cells of susceptible and resistant mice responded equally to a mitogenic stimulus, but only lymph node cells from alopecia areata affected mice displayed an increased response with T cell receptor stimulation via anti-CD3 cross-linking. These results suggest alopecia areata is a cell-mediated autoimmune disease, but alopecia areata affected skin graft hosts may resist alopecia areata onset through active counter-regulatory mechanisms. Because alopecia areata resistant mice showed unimpaired responsiveness and a transient inflammatory response towards the graft, it is suggested that alopecia areata develops as a consequence of an inappropriate immune response regulation.