Distorted antigen-presenting function of Langerhans cells induced by tumor necrosis factor α via a mechanism that appears different from that induced by ultraviolet B radiation

J. C. Simon, D. Edelbaum, P. R. Bergstresser, Ponciano D Cruz

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9 Scopus citations

Abstract

Tumor necrosis factor α (TNFα) has been shown to mimic 2 effects of ultraviolet B (UVB) radiation in mice: morphologic damage to epidermal Langerhans cells (LC) and the inability to mount a normal contact hypersensitivity (CH) response. Our previous studies have shown LC to be the target of the immune tolerance evoked by UVB radiation, both during induction of CH in vivo and during presentation of protein antigen to CD4+ Th1 cells (Th1) in vitro. To determine whether these influences of TNFα and of UVB radiation on LC are related, 2 sets of experiments were performed. We first examined the effect of recombinant TNFα on the capacity of epidermal cells enriched for LC (IEC) to present keyhole limpet hemocyanin (KLH) to KLH-specific and Ia(d)-restricted Th1. Addition of TNFα to co-cultures of IEC and Th1 significantly reduced proliferation in a dose-dependent manner.This inhibition was specific since it was reversed by neutralizing Ab against TNFα. That TNFα blocked Th1 proliferation by acting directly on LC is supported by 2 findings: 1) selective treatment of IEC prior to co-culturing also led to failure to present KLH; and 2) TNFα did not reduce Th1 proliferation stimulated by phorbol myristate acetate plus ionomycin, or by IL-2. We next examined the capacity of anti-TNFα Ab to protect LC from loss of antigen-presenting cell (APC) function induced by a single dose of 200 J/m2 UVB. Anti-TNFα Ab tested over a broad dose range did not prevent or restore the ability of UVB-irradiated IEC to present KLH to Th1. We conclude that TNFα can abrogate the APC function of LC through a mechanism that appears different from that which occurs following UVB radiation.

Original languageEnglish (US)
Pages (from-to)190-194
Number of pages5
JournalPhotodermatology Photoimmunology and Photomedicine
Volume8
Issue number5
StatePublished - Dec 1 1991

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Radiology Nuclear Medicine and imaging
  • Dermatology

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