Infiltration of cytotoxic T cells in drug-induced cutaneous eruptions
Article first published online: 24 DEC 2001
Clinical & Experimental Allergy
Volume 30, Issue 6, pages 847–855, June 2000
How to Cite
Yawalkar, Egli, Hari, Nievergelt, Braathen and Pichler (2000), Infiltration of cytotoxic T cells in drug-induced cutaneous eruptions. Clinical & Experimental Allergy, 30: 847–855. doi: 10.1046/j.1365-2222.2000.00847.x
- Issue published online: 24 DEC 2001
- Article first published online: 24 DEC 2001
- drug allergy;
- granzyme B;
Previous in vitro data indicate that perforin containing drug-specific cytotoxic T cells are involved in cutaneous drug reactions.
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)-γ, which are known to stimulate cytotoxic T cells, was investigated.
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 IFNγ was analysed using immunohistochemistry.
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 IFNγ was observed in the mononuclear cells infiltrate, indicating that these cytokines may be important in activation of these cytotoxic T cells.
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.