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. CONCLUSION: 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.
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. CONCLUSION: 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: Barbara Lotti; Thomas Wendland; Hansjakob Furrer; Nikhil Yawalkar; Salome von Greyerz; Karin Schnyder; Marlène Brandes; Pietro Vernazza; Ralf Wagner; Thi Nguyen; Eric Rosenberg; Werner J Pichler; Christian Brander Journal: J Clin Immunol Date: 2002-09 Impact factor: 8.317
Authors: Simone Schmid; Petra C Kuechler; Markus Britschgi; Urs C Steiner; Nikhil Yawalkar; Alain Limat; Kurt Baltensperger; Lasse Braathen; Werner J Pichler Journal: Am J Pathol Date: 2002-12 Impact factor: 4.307
Authors: N Yawalkar; R E Hunger; C Buri; S Schmid; F Egli; C U Brand; C Mueller; W J Pichler; L R Braathen Journal: Am J Pathol Date: 2001-03 Impact factor: 4.307
Authors: M Britschgi; U C Steiner; S Schmid; J P Depta; G Senti; A Bircher; C Burkhart; N Yawalkar; W J Pichler Journal: J Clin Invest Date: 2001-06 Impact factor: 14.808