title: Expansion of vitiligo lesions is associated with reduced epidermal CDw60 expression and increased expression of HLA-DR in perilesional skin.
abstract: BACKGROUND
  Detection of CDw60 in skin is representative of ganglioside D3 expression. This ganglioside is expressed primarily by melanocytes, and is of interest as a membrane antigen targeted by immunotherapy for melanoma patients. Expression of CDw60 by keratinocytes is defined by the presence of T-helper cell (Th)1 vs. Th2 cytokines, and can serve as a sentinel molecule to characterize an ongoing skin immune response.
  
  
  OBJECTIVE
  These immunobiological characteristics have provided the incentive to study the expression of CDw60 in the context of progressive vitiligo.
  
  
  METHODS
  Frozen sections were obtained from control skin and from vitiligo lesions and immunostained to show CDw60. Cells were cultured, their CDw60 expression studied and ribonuclease protection assays run to detect cytokine mRNA.
  
  
  RESULTS
  Resistance to cytokine-mediated regulation of CDw60 expression was demonstrated in vitro by melanocytes, which appeared capable of generating autocrine and paracrine regulatory molecules supporting CDw60 expression. Induction of CDw60 expression was inhibited by antibodies to interleukin (IL)-4, suggesting that this cytokine was responsible, at least in part, for melanocyte-induced CDw60 expression. Marginal skin from patients with progressive generalized vitiligo consistently showed a reduction in epidermal CDw60 expression alongside elevated human leucocyte associated antigen (HLA)-DR expression at the margin. It thus appears that inflammatory infiltrates present in marginal skin generate type 1 rather than type 2 cytokines, supportive of a cell-mediated autoimmune response.
  
  
  CONCLUSIONS
  These results support an active role of melanocytes within the skin immune system, and associate their loss in generalized vitiligo with a cell-mediated immune response mediated by type 1 cytokines.
authors: Department of Pathology, Cardinal Bernardin Cancer Center Rm 203, Loyola University, 2160 South First Avenue, Maywood, Chicago, IL 60153, U.S.A. ilepool@lumc.edu
authors: I C
authors: IC
authors: Le Poole
authors: L S
authors: LS
authors: Stennett
authors: B K
authors: BK
authors: Bonish
authors: L
authors: L
authors: Dee
authors: J K
authors: JK
authors: Robinson
authors: C
authors: C
authors: Hernandez
authors: S K
authors: SK
authors: Hann
authors: B J
authors: BJ
authors: Nickoloff
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D018450:Disease Progression; D004817:Epidermis / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005732:Gangliosides / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D015847:Interleukin-4 / Q000096:biosynthesis; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D008544:Melanocytes / Q000276:immunology; D008875:Middle Aged; D014820:Vitiligo / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C064741:CDw60 antigen; D017077:Culture Media, Conditioned; D005732:Gangliosides; D006684:HLA-DR Antigens; D015847:Interleukin-4; C026226:ganglioside, GD3