Submitted to: Avian Immunology Research Group Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 9/10/2002
Publication Date: N/A
Technical Abstract: Vitiligo is a common acquired hypopigmentary disorder characterized by a loss of epidermal pigment cells (melanocytes). The Smyth line (SL) chicken is the only animal model for autoimmune vitiligo that recapitulates the entire spectrum of clinical and biological manifestations of the human disease. Phenotypic analysis of lymphocytes present in feathers (site of melanocyte destruction) and immunosuppression studies strongly suggested an important role of cell-mediated immunity (CMI) in the development of SL vitiligo (SLV). To further examine a role of CMI in SLV, SL chickens with SLV and normally pigmented SL and control lines of chickens were injected into the wattle with melanocyte lysates to determine the delayed wattle swelling response (DWR). The DWR was only observed in SL chickens with SLV and not in normally pigmented individuals. Immunohistochemical staining of wattle tissue revealed extensive lymphocyte infiltration (primarily TCR2+, CD4+ or CD8+ T cells) in DWR+ wattles. These observations support the presence of melanocyte-specific CMI in SL chickens with vitiligo. As interferon gamma (IFN-gamma) is an important cytokine released during a CMI response, IFN-gamma expression and production was examined in feathers by Northern blotting with an antisense chicken (Ch) IFN-gamma-specific digoxigenin-labeled riboprobe and by immunoblotting with anti-ChIFN-gamma monoclonal antibody (6D3). IFN-gamma was detected in feather samples with actively developing depigmentation. In contrast, IFN-gamma was low or near undetectable levels prior to noticeable depigmentation or after complete depigmentation. In normally pigmented chickens, IFN-gamma was not detected in feather tissue. A role of INF-gamma in the expression of SLV was also shown when injection of recombinant ChINF-gamma twice per week for the first 6 weeks of life induced expression of SLV in 7 of 8 female SL chicks. The incidence in female SL chicks injected with control vehicle was 25%. Taken together, these observations strongly support a role of a Th1 dominated CMI response in the loss of melanocytes in SLV.