Journal article
Epidermal HLA-DR and the enhancement of cutaneous reactivity to superantigenic toxins in psoriasis
The Journal of clinical investigation, Vol.104(9), pp.1181-1189
11/01/1999
DOI: 10.1172/JCI6835
PMCID: PMC409817
PMID: 10545517
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.
Details
- Title: Subtitle
- Epidermal HLA-DR and the enhancement of cutaneous reactivity to superantigenic toxins in psoriasis
- Creators
- Jeffrey B Travers - Division of Pediatric Allergy and Immunology, The National Jewish Medical and Research Center, Denver, Colorado 80206, USAQutayba A Hamid - Division of Pediatric Allergy and Immunology, The National Jewish Medical and Research Center, Denver, Colorado 80206, USADavid A Norris - Division of Pediatric Allergy and Immunology, The National Jewish Medical and Research Center, Denver, Colorado 80206, USAChristine Kuhn - Division of Pediatric Allergy and Immunology, The National Jewish Medical and Research Center, Denver, Colorado 80206, USARalph C Giorno - Division of Pediatric Allergy and Immunology, The National Jewish Medical and Research Center, Denver, Colorado 80206, USAPatrick M Schlievert - Division of Pediatric Allergy and Immunology, The National Jewish Medical and Research Center, Denver, Colorado 80206, USAEvan R Farmer - Division of Pediatric Allergy and Immunology, The National Jewish Medical and Research Center, Denver, Colorado 80206, USADonald Y.M Leung - Division of Pediatric Allergy and Immunology, The National Jewish Medical and Research Center, Denver, Colorado 80206, USA
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.104(9), pp.1181-1189
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/JCI6835
- PMID
- 10545517
- PMCID
- PMC409817
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 11/01/1999
- Academic Unit
- Microbiology and Immunology; Internal Medicine
- Record Identifier
- 9984001139702771
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