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Death ligand TRAIL, secreted by CD1a+ and CD14+ cells in blister fluids, is involved in killing keratinocytes in toxic epidermal necrolysis
Author(s) -
de Araujo Elisabeth,
Dessirier Valérie,
Laprée Geneviève,
ValeyrieAllanore Laurence,
Ortonne Nicolas,
Stathopoulos Efstathios N.,
Bagot Martine,
Bensussan Armand,
Mockenhaupt Maja,
Roujeau JeanClaude,
Tsapis Andreas
Publication year - 2011
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2010.01176.x
Subject(s) - cytotoxic t cell , granulysin , keratinocyte , immunology , perforin , granzyme , toxic epidermal necrolysis , cd8 , chemistry , biology , in vitro , antigen , biochemistry , genetics
Toxic epidermal necrolysis (TEN) is characterized by an acute detachment and destruction of keratinocytes, affecting large areas of the skin. It is often related to adverse drug reactions. Previous studies have shown that effector CD8+ T cells, which accumulate in the blister fluid, are functionally cytotoxic and act through a classical perforin/granzyme B pathway. It has recently been shown that these cytotoxic T cells also secrete granulysin peptide, which is lethal to keratinocytes. These cytotoxic T cells exert their killer activity against autologous keratinocytes in the presence of the drug. However, they are unlikely to be the only effectors of TEN. We therefore searched for soluble death factors in the blister fluids that might kill keratinocytes. We found that the amounts of interferon‐γ, TRAIL and TNF‐α proteins were significantly greater in TEN blister fluids than in all controls (normal sera, TEN sera, burns and Eosinophilic pustular folliculitis blister fluids) and TNF‐like weak inducer of apoptosis (TWEAK) amounts are also greater in all controls except burns. We showed that these proteins acted in synergy to induce the death of keratinocytes in vitro . We also found that TRAIL and TWEAK were secreted by CD1a+ and CD14+ cells present in the blister fluids. Thus, in addition to MHC class I‐restricted cytotoxic T lymphocytes (CTLs), which lyse keratinocytes, ligands secreted by non‐lymphoid cells capable of inducing keratinocyte death in an MHC class I‐independent manner, also seem to be present in the blister fluids of patients with TEN.