title: Possible involvement of CD14+ CD16+ monocyte lineage cells in the epidermal damage of Stevens-Johnson syndrome and toxic epidermal necrolysis.
abstract: BACKGROUND
  Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are characterized by keratinocyte apoptosis and necrosis, resulting in epidermal detachment. Although monocytes abundantly infiltrate the epidermis in SJS/TEN skin lesions, the properties and functions of these cells have not been fully examined.
  
  
  OBJECTIVE
  To determine the properties of monocytes infiltrating into the epidermis in SJS/TEN.
  
  
  METHODS
  Immunostaining of skin sections was performed to examine the membrane markers of monocytes infiltrating into skin lesions.
  
  
  RESULTS
  Immunostaining of cryosections from 11 SJS/TEN skin lesions revealed numerous CD14+ monocytes located along the dermoepidermal junction and throughout the epidermis. The cells coexpressed CD16, CD11c and HLA-DR. CD14+ CD16+ cells were identified in very early lesions without epidermal damage, suggesting that their infiltration is a cause, rather than a result, of epidermal damage. Moreover, these cells expressed CD80, CD86 and CD137 ligand, indicative of their ability to facilitate the proliferation and cytotoxicity of CD8+ T cells. CD16+ cells infiltrating the epidermis and detected at the dermoepidermal junction were immunostained and counted in paraffin-embedded skin sections obtained from 47 patients with drug rash manifested as TEN, SJS, maculopapular-type rash or erythema multiform-type rash. The number of CD16+ monocytes infiltrating the epidermis increased significantly, depending on the grade of epidermal damage.
  
  
  CONCLUSIONS
  These findings suggest that the appearance of CD14+ CD16+ cells of monocyte lineage plays an important role in the epidermal damage associated with SJS/TEN, most probably by enhancing the cytotoxicity of CD8+ T cells.
authors.affiliation: Department of Dermatology, Ehime University Graduate School of Medicine, Shitsukawa, Toon-city, Ehime 791-0295, Japan. tohm@m.ehime-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Tohyama
authors.forename: H
authors.initials: H
authors.lastname: Watanabe
authors.forename: S
authors.initials: S
authors.lastname: Murakami
authors.forename: Y
authors.initials: Y
authors.lastname: Shirakata
authors.forename: K
authors.initials: K
authors.lastname: Sayama
authors.forename: M
authors.initials: M
authors.lastname: Iijima
authors.forename: K
authors.initials: K
authors.lastname: Hashimoto
mesh_terms: D053330:4-1BB Ligand / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D019070:Cell Lineage; D049109:Cell Proliferation; D004817:Epidermis / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000473:pathology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism*; D013262:Stevens-Johnson Syndrome / Q000276:immunology / Q000473:pathology*
chemical_list: D053330:4-1BB Ligand; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; C505974:TNFSF9 protein, human