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The goal of this study was to determine the role of Fas-mediated apoptosis in human epidermal aging. Epidermal Fas expression and apoptosis are increased in aged human skin. Aging changes of human epidermis, including decreased epidermal thickness and proliferation, are reversed following grafting of human skin to SCID (severe combined immunodeficiency) mice. Skin from aged participants (n = 14; mean 70.7 years), and young participants (n = 14; mean 23.4 years) was grafted to beige SCID mice, and epidermal thickness, proliferation (Ki-67 expression), apoptosis (TUNEL [Tdt-mediated dUTP nick end labeling] reaction below granular layer), and expression of Fas and FasL were determined by histology and immunochemical staining. Aged skin was associated with thinning of the epidermis, decreased epidermal proliferation, a significant increase in apoptosis below the granular layer, and epidermal Fas expression. Engraftment significantly reversed these aging changes, including apoptosis, and Fas expression. Correlation of reversal of aging changes, with decreased epidermal Fas expression and apoptosis, supports a role for Fas-mediated apoptosis in aging of human epidermis.

Objective: To determine the role of CD4[sup +] and CD8[sup +] T lymphocytes in the pathogenesis of alopecia areata. Design: Relapse of alopecia areata was induced in autologous human scalp grafts on Prkdc[sup scid] mice by injection of activated T lymphocytes derived from lesional skin. CD4[sup +] and CD8[sup +] T cells were separated by magnetic beads before injection. Setting: University-based dermatology practice. Participants: Eleven patients with either alopecia totalis or severe alopecia areata. Main Outcome Measures: Hair regrowth, hair loss, and immunohistochemical findings of scalp explants. Intervention: Transfer of scalp T cells to autologous lesional scalp explants on Prkdc[sup scid] mice. Results: Injection of unseparated T cells and mixed CD4[sup +] plus CD8[sup +] T cells resulted in significant hair loss (P<.01) in 5 of 5 experiments. However, injection of purified CD4[sup +] or CD8[sup +] T cells alone did not result in reproducible hair loss. CD4[sup +] and CD8[sup +] T cells induced follicular expression of intercellular adhesion molecule 1 (CD54), HLA-DR, and HLA-A, HLA-B, and HLA-C after injection into scalp grafts. Conclusions: CD4[sup +] and CD8[sup +] T cells have a role in the pathogenesis of alopecia areata. It is hypothesized that CD8[sup +] T cells act as the effector cells, with CD4[sup +] T cell help. It is now necessary to look for HLA-A, HLA-B, and HLA-C associations with alopecia areata. Therapeutic manipulations that interfere with CD8[sup +] activity should be examined. [ABSTRACT FROM AUTHOR]

Alopecia areata is an autoimmune condition directed at hair follicles, which results in loss of hair. We have previously demonstrated that it is possible to transfer hair loss, along with the immunohistologic findings of alopecia areata, to human scalp grafts on Prkdcscid (SCID) mice by injection of autologous activated lesional T-cells. This study examines the cytokine profile of T-cells and follicular epithelium following transfer of hair loss. Two consistent findings significantly (P < 0.01) associated with hair loss were production of interferon-γ-inducible protein-10kDa (IP-10) by follicular epithelium (13/13), and production of INF-γ by infiltrating T-cells (10/12). Noninjected control grafts regrew hair, and were generally negative for IP-10 (positive 2/9), and INF-γ (positive 2/9), but expressed of IL-10 on the follicular epithelium (7/9). These data support an INF-γ TH1 pathogenesis for hair loss in alopecia areata. [Copyright &y& Elsevier]

Alopecia areata is a tissue restricted autoimmune condition affecting the hair follicle, resulting in hair loss. The goal of this study was to test the hypothesis that the autoantigen of alopecia areata is melanocyte associated. Potential autoantigens were tested in the human scalp explant/Prkdscid CB-17 mouse transfer system. Scalp T cells from lesional (bald) alopecia areata scalp were cultured with antigen-presenting cells, and antigen, along with interleukin-2. The T cells were then injected into autologous lesional scalp grafts on SCID mice, and hair regrowth was measured. Hair follicle homogenate was used as an autoantigen control. T cells cultured with melanoma homogenate induced statistically significant reduction in hair growth (p < 0.01 by ANOVA). HLA-A2-restricted melanocyte peptide epitopes were then tested with lesional scalp T cells from HLA-A2-positive alopecia areata patients. Melanocyte-peptide-activated T cells significantly reduced the number of hairs regrowing in two experiments with six patients (p < 0.001 by ANOVA). Injected scalp grafts showed histologic and immunochemical changes of alopecia areata. The most consistent peptide autoantigens were the Gp100-derived G9-209 and G9-280 peptides, as well as MART-1 (27–35). Melanocyte peptide epitopes can function as autoantigens for alopecia areata. Multiple peptides were recognized, suggesting epitope spreading. [ABSTRACT FROM AUTHOR]