title: Infiltration of cytotoxic T cells in drug-induced cutaneous eruptions.
abstract: BACKGROUND
  Previous in vitro data indicate that perforin containing drug-specific cytotoxic T cells are involved in cutaneous drug reactions.
  
  
  OBJECTIVE
  The aim of this study was to investigate the in situ expression of perforin and granzyme B together with the nature of the inflammatory infiltrate in acute drug-induced exanthem. Furthermore, expression of interleukin (IL)-12 and interferon (IFN)-gamma, which are known to stimulate cytotoxic T cells, was investigated.
  
  
  METHODS
  Skin biopsy specimens were obtained from 10 patients with a generalized maculopapular exanthem and from nine controls with normal skin. Expression of CD3, CD4, CD8, CD56, CD1a, CD68, CD25, HLA-DR, CD54, perforin, granzyme B, IL-12 and IFNgamma was analysed using immunohistochemistry.
  
  
  RESULTS
  In contrast to the controls, the skin of patients with an exanthem was mainly infiltrated by T cells (CD4 > CD8) and showed a marked enhancement of perforin and granzyme B immunostaining. Double immunostaining revealed that perforin and granzyme B were expressed in both CD4+ and CD8+ cells, which were partly located at the dermoepidermal junction and in the epidermis. In addition, strong immunreactivity for IL-12 and IFNgamma was observed in the mononuclear cells infiltrate, indicating that these cytokines may be important in activation of these cytotoxic T cells.
  
  
  CONCLUSIONS
  The increased numbers of perforin and granzyme B containing T cells infiltrating the dermoepidermal junction may contribute to the damage of epidermal cells, which is frequently observed as a typical feature of interface dermatitis in drug-induced exanthem. Our data provide further evidence that cytotoxic T cells play an essential role in cutaneous drug reactions.
authors.affiliation: Clinic for Rheumatology and Clinical Immunology/Allergology, Department of Dermatology, University of Bern, 3010 Bern, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Yawalkar
authors.forename: F
authors.initials: F
authors.lastname: Egli
authors.forename: Y
authors.initials: Y
authors.lastname: Hari
authors.forename: H
authors.initials: H
authors.lastname: Nievergelt
authors.forename: L R
authors.initials: LR
authors.lastname: Braathen
authors.forename: W J
authors.initials: WJ
authors.lastname: Pichler
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003875:Drug Eruptions / Q000276:immunology*; D005076:Exanthema / Q000139:chemically induced* / Q000276:immunology*; D005260:Female; D053804:Granzymes; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D018664:Interleukin-12; D007371:Interferon-gamma; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases