Distorted antigen-presenting function of Langerhans cells induced by tumor necrosis factor alpha via a mechanism that appears different from that induced by ultraviolet B radiation.
Tumor necrosis factor alpha (TNF alpha) 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 TNF alpha and of UVB radiation on LC are related, 2 sets of experiments were performed. We first examined the effect of recombinant TNF alpha on the capacity of epidermal cells enriched for LC (IEC) to present keyhole limpet hemocyanin (KLH) to KLH-specific and Iad-restricted Th1. Addition of TNF alpha 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 TNF alpha. That TNF alpha 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) TNF alpha did not reduce Th1 proliferation stimulated by phorbol myristate acetate plus ionomycin, or by IL-2. We next examined the capacity of anti-TNF alpha Ab to protect LC from loss of antigen-presenting cell (APC) function induced by a single dose of 200 J/m2 UVB. Anti-TNF alpha Ab tested over a broad dose range did not prevent or restore the ability of UVB-irradiated IEC to present KLH to Th1.(ABSTRACT TRUNCATED AT 250 WORDS)
Simon
J C
JC
Department of Dermatology, University of Texas Southwestern Medical Center, Dallas 75235-9069.
Edelbaum
D
D
Bergstresser
P R
PR
Cruz
P D
PD
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002455:Cell Division; D002478:Cells, Cultured; D005260:Female; D007801:Langerhans Cells / Q000276:immunology* / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D012867:Skin / Q000166:cytology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D014466:Ultraviolet Rays
D014409:Tumor Necrosis Factor-alpha