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.

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: N Yawalkar, F Egli, Y Hari, H Nievergelt, L R Braathen, W J Pichler
• Journal: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology (Clin Exp Allergy) Vol. 30 Issue 6 Pg. 847-55 (Jun 2000) ISSN: 0954-7894 [Print] England
• PMID: 10848903 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Membrane Glycoproteins
• Pore Forming Cytotoxic Proteins
• Perforin
• Interleukin-12
• Interferon-gamma
• GZMB protein, human
• Granzymes
• Serine Endopeptidases

Topics

• Adult
• Aged
• Antigens, CD (analysis)
• CD4-Positive T-Lymphocytes (immunology)
• Drug Eruptions (immunology)
• Exanthema (chemically induced, immunology)
• Female
• Granzymes
• Humans
• Immunohistochemistry
• Immunophenotyping
• Interferon-gamma (metabolism)
• Interleukin-12 (metabolism)
• Male
• Membrane Glycoproteins (metabolism)
• Middle Aged
• Perforin
• Pore Forming Cytotoxic Proteins
• Serine Endopeptidases (metabolism)
• T-Lymphocyte Subsets (immunology)
• T-Lymphocytes, Cytotoxic (immunology, metabolism)