Blister fluid T lymphocytes during toxic epidermal necrolysis are functional cytotoxic cells which express human natural killer (NK) inhibitory receptors

Abstract

SUMMARYToxic epidermal necrolysis (TEN) is a rare life-threatening adverse drug reaction characterized by a massive destruction of the epidermis. Immunohistological studies of skin biopsies of TEN showed infiltrates of predominantly CD8 þ T lymphocytes even though other authors reported a prominent involvement of cells of the monocyte-macrophage lineage. The aim of this study was to characterize phenotypically and functionally the cells present in the cutaneous blister fluid of four patients with TEN. We first determined that lymphocytes were predominant in blister fluid obtained early, while monocytes/macrophages later became the most important population. We then showed that this lymphocyte population, mainly CD3 þ CD8 þ , corresponded to a peculiar cell subset as they expressed cutaneous leucocyte antigen, killer inhibitory receptors KIR/KAR and failed to express CD28 molecule. Functionally, we determined that blister T lymphocytes had a cytotoxic T lymphocyte (CTL)-and NKlike cytotoxicity. The role of this cytotoxic lymphocyte population present at the site of lesions during TEN remains to be understood.

Defective Regulatory T Cells In Patients with Severe Drug Eruptions: Timing of the Dysfunction Is Associated with the Pathological Phenotype and Outcome

“…Goat F(abЈ) 2 anti-human IgG Fc was purchased from Beckman Coulter. mAbs to human CD3 (HIT3a), forkhead box P3 (Foxp3; PCH101), and the isotype controls to Foxp3 were purchased from eBioscience.…”

“…Although many factors that cause variability in the clinical course have been suggested, it remains unknown which factors are predominantly involved in the process. Because the most prevalent severe drug eruptions are thought to be mediated by drug-reactive T cells (1)(2)(3)(4), the phenotype and functions of these effector T cells are likely to determine the clinical picture of the disease. However, investigators need to be made aware of the alternative view that severe drug eruptions are due to a dysbalance of the immune system caused by excessive activation of effector T cells and an inadequately low function or number of T cells that can limit immunopathology.…”

Toxic Epidermal Necrolysis Like Bullous Skin Reaction: An Autopsy Case

“…2002 yılında bildirdikleri olguda bül sıvısı içerisinde lenfosit ağırlık-lı hücresel dağılım bulunduğu-nu bildirmişlerdir. T lenfositleri arasında da en sık CD3+ ve CD8+ ağırlıklı oldukları bildirilmiştir (10,11).…”

Immunohistochemical Expression of Apoptotic Markers in Drug-Induced Erythema Multiforme, Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

“…Prior reports that used immunolabeling to characterize the effector cells ofthe epidermal injury in SJS/TEN obtained conflicting results (13,(17)(18). It is conceivable that CD8+ T lymphocytes are important in initiating the death ofkeratinocytes in SJSI TEN (19), while monocyte-macrophage populations playa pivotal role at the late stage of SJS/TEN. In our study, we found that the epidermal infiltrate was predominantly composed of CD8+ T lymphocytes, this finding confirming the skin biopsy specimens taken at early stage of disease.…”