Tumor necrosis factor-alpha impairs contact hypersensitivity induction after ultraviolet B radiation via TNF-receptor 2 (p75).
Acute, low dose ultraviolet B radiation (UVR) impairs induction of contact hypersensitivity (CH) in genetically susceptible mice. Polymorphic alleles at the TNF-alpha locus dictate the susceptibility phenotype, and neutralizing anti-TNF-alpha antibodies restore CH induction in mice exposed to UVR. This circumstantial evidence strongly implicates TNF-alpha in the pathogenesis of failed CH induction after UVR. Using mice genetically deficient in TNF-receptor 1 (p55) or TNF-receptor 2 (p75), we now report that the capacity of TNF-alpha to impair CH induction after UVR required signaling via TNF-receptor 2, rather than TNF-receptor 1. Moreover, acting via the same receptor, TNF-alpha altered the density and morphology of class II MHC-bearing epidermal Langerhans cells. However, UVR retained its capacity to induce tolerance in both TNF-receptor 1 and TNF-receptor 2 deficient mice, indicating that TNF-alpha plays no role in the systemic immune deficit created by UVR.
Kurimoto
I
I
The Schepens Eye Research Institute and Department of Dermatology, Harvard Medical School, Boston, Massachusetts 02114, USA.
Streilein
J W
JW
D000483:Alleles; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D003877:Dermatitis, Contact / Q000209:etiology* / Q000517:prevention & control*; D007108:Immune Tolerance / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009500:Neutralization Tests; D010641:Phenotype; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology*; D047889:Receptors, Tumor Necrosis Factor, Type II; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha