RESUMO
The most severe form of virus-induced inflammation at the ocular surface is epidemic keratoconjunctivitis (EKC), often caused by group D human adenoviruses (HAdVs). We investigated the dynamics and mechanisms of changes in natural killer (NK) cell types in the human ocular mucosal surface in situ over the course of infection. In the acute phase of infection, the mature CD56(dim)NK cells that comprise a major subpopulation in the normal human conjunctiva are replaced by CD56(bright)NK cells recruited to the ocular surface by chemokines produced by the infected epithelium, and NKG2A-expressing CD56(dim) and CD56(bright) NK cells become the major subpopulations in severe inflammation. These NK cells attracted to the mucosal surface are however incapable of mounting a strong antiviral response because of upregulation of the inhibitory ligand human leukocyte antigen-E (HLA-E) on infected epithelium. Furthermore, group D HAdVs downregulate ligands for activating NK cell receptors, thus rendering even the mature NKG2A(-)NK cells unresponsive, an immune-escape mechanism distinct from other adenoviruses. Our findings imply that the EKC-causing group D HAdVs utilize these multiple pathways to inhibit antiviral NK cell responses in the initial stages of the infection.
Assuntos
Infecções por Adenoviridae/imunologia , Túnica Conjuntiva/imunologia , Conjuntivite Viral/imunologia , Evasão da Resposta Imune , Células Matadoras Naturais/imunologia , Mucosa/imunologia , Adenoviridae/imunologia , Adenoviridae/patogenicidade , Infecções por Adenoviridae/genética , Infecções por Adenoviridae/patologia , Infecções por Adenoviridae/virologia , Antígeno CD56/genética , Antígeno CD56/imunologia , Linhagem Celular Tumoral , Quimiocinas/genética , Quimiocinas/imunologia , Quimiocinas/farmacologia , Quimiotaxia/efeitos dos fármacos , Técnicas de Cocultura , Túnica Conjuntiva/patologia , Túnica Conjuntiva/virologia , Conjuntivite Viral/genética , Conjuntivite Viral/patologia , Conjuntivite Viral/virologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Células Epiteliais/patologia , Células Epiteliais/virologia , Regulação da Expressão Gênica , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/patologia , Células Matadoras Naturais/virologia , Mucosa/patologia , Mucosa/virologia , Subfamília C de Receptores Semelhantes a Lectina de Células NK/genética , Subfamília C de Receptores Semelhantes a Lectina de Células NK/imunologia , Cultura Primária de Células , Índice de Gravidade de Doença , Transdução de Sinais , Lágrimas/química , Antígenos HLA-ERESUMO
AIMS: To evaluate glucose tolerance of patients with Vogt-Koyanagi-Harada (VKH) disease before systemic corticosteroid therapy, and to assess changes brought on by treatment. METHODS: 20 VKH patients with acute bilateral panuveitis were studied. 20 healthy adults and 11 Behçet's disease patients with active uveoretinitis served as controls. A 75 g oral glucose tolerance test (OGTT) was given in the acute stage of ocular inflammation before systemic corticosteroid therapy. The OGTT was repeated in the convalescent stage of VKH disease in the patients with glucose intolerance before treatment. Insulin response was examined at the same time as the OGTT when possible. RESULTS: 55% of VKH patients (11/20) showed glucose intolerance but no apparent insulin secretion deficiency was detected. Four of seven patients in the convalescent stage showed improvement of glucose tolerance. None of the normal controls or disease controls showed glucose intolerance. CONCLUSION: A high incidence of glucose intolerance was found in the acute stage of VKH disease. However, glucose intolerance improved in most cases after systemic corticosteroid therapy. It is possible that glucose intolerance seen in VKH patients may be related to the autoimmune inflammatory process of this disease.
