title: Immunohistochemical examination of the role of Fas ligand and lymphocytes in the pathogenesis of human liver yellow fever.
abstract: Yellow fever is an infectious, non-contagious disease caused by an RNA virus of the family Flaviviridae, which is transmitted to man by the bite of hematophagous mosquitoes. Infection with the yellow fever virus can progress with lesions in the heart, kidneys, central nervous system, and liver. In the liver, the histopathological picture is characterized by necrosis, steatosis and hepatocyte apoptosis, with a preferential midzone distribution. In the present study, liver samples from fatal patients with yellow fever were analyzed. The histopathological pattern was characterized by steatosis, lytic necrosis and hepatocyte apoptosis associated with a moderate mononuclear inflammatory infiltrate. The inflammatory component mainly consisted of CD4+ T lymphocytes, followed by CD8+ T lymphocytes, which showed a preferential portal and midzone distribution. Immunoreactivity to Fas ligand was mainly observed in hepatocytes of the midzone region. Based on these findings, we conclude that lymphocytes play an important role in the genesis of hepatic lesions in severe yellow fever, inducing hepatocyte apoptosis through the binding to Fas receptors. However, further studies are necessary to investigate the participation of other immune factors and to quantify the role of the cytotoxic cellular response in the lesion evolution during the course of disease in the liver.
authors.affiliation: Núcleo de Medicina Tropical, Universidade Federal do Pará, Av. Generalissimo Deodoro 92, 66055-240, Belém, Pará, Brazil. juarez@ufpa.br
authors.forename: Juarez Antonio Simões
authors.initials: JA
authors.lastname: Quaresma
authors.forename: Vera Lucia Reis Souza
authors.initials: VL
authors.lastname: Barros
authors.forename: Elaine Raniero
authors.initials: ER
authors.lastname: Fernandes
authors.forename: Carla
authors.initials: C
authors.lastname: Pagliari
authors.forename: Fernanda
authors.initials: F
authors.lastname: Guedes
authors.forename: Pedro Fernando
authors.initials: PF
authors.lastname: da Costa Vasconcelos
authors.forename: Heitor Franco
authors.initials: HF
authors.lastname: de Andrade Junior
authors.forename: Maria Irma Seixas
authors.initials: MI
authors.lastname: Duarte
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D053222:Fas Ligand Protein; D005234:Fatty Liver / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008099:Liver / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D008875:Middle Aged; D009336:Necrosis; D010784:Photomicrography; D048069:Tumor Necrosis Factors / Q000276:immunology*; D015004:Yellow Fever / Q000276:immunology*
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D048069:Tumor Necrosis Factors