Epidermal HLA-DR and the enhancement of cutaneous reactivity to superantigenic toxins in psoriasis

Jeffrey B. Travers, Qutayba A. Hamid, David A. Norris, Christine Kuhn, Ralph C. Giorno, Patrick M. Schlievert, Evan R. Farmer, Donald Y.M. Leung

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Streptococcal and staphylococcal superantigens (SAg's) have been implicated in the pathogenesis of inflammatory skin diseases, but the mechanisms by which these toxins act are unknown. The present study assessed the ability of nanogram quantities of topically applied purified toxic shock syndrome toxin-1 (TSST-1), staphylococcal enterotoxin type B, and streptococcal pyrogenic enterotoxin types A and C to induce inflammatory reactions in clinically uninvolved skin of normal controls and subjects with psoriasis, atopic dermatitis, and lichen planus. These SAg's triggered a significantly greater inflammatory skin response in psoriatics than in normal control subjects or in subjects with atopic dermatitis or lichen planus. Surprisingly, skin biopsies did not exhibit the T-cell receptor Vβ stimulatory properties predicted for SAg-induced skin reactions. By 6 hours after patch testing with SAg's, TNF-α mRNA had increased in the epidermis (but not the dermis) in biopsies from psoriatics, compared with controls. Immunohistochemical studies revealed significantly higher HLA-DR expression in keratinocytes from psoriatics than from controls. However, a mutant TSST-1 protein that fails to bind HLA-DR did not elicit an inflammatory skin reaction. These results indicate that keratinocyte expression of HLA-DR enhances inflammatory skin responses to SAg's. They may also account for previous studies failing to demonstrate selective expansion of T-cell receptor Vβs in psoriatics colonized with SAg-producing Staphylococcus aureus, and they identify a novel T cell-independent mechanism by which SAg's contribute to the pathogenesis of inflammatory skin diseases.

Original languageEnglish (US)
Pages (from-to)1181-1189
Number of pages9
JournalJournal of Clinical Investigation
Volume104
Issue number9
DOIs
StatePublished - Nov 1999

ASJC Scopus subject areas

  • Medicine(all)

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