title: TAM receptor knockout mice are susceptible to retinal autoimmune induction.
abstract: OBJECTIVE
  TAM receptors are expressed mainly by dendritic cells and macrophages in the immune system, and mice lacking TAM receptors develop systemic autoimmune diseases because of inefficient negative control of the cytokine signaling in those cells. This study aims to test the susceptibility of the TAM triple knockout (tko) mice to the retina-specific autoantigen to develop experimental autoimmune uveoretinitis (EAU).
  
  
  METHODS
  TAM tko mice that were or were not immunized with interphotoreceptor retinoid-binding protein (IRBP) peptides were evaluated for retinal infiltration of the macrophages and CD3(+) T cells by immunohistochemistry, spontaneous activation of CD4(+) T cells, and memory T cells by flow cytometry and proliferation of IRBP-specific CD4(+) T cells by [(3)H]thymidine incorporation assay. Ocular inflammation induced by IRBP peptide immunization and specific T cell transfer were observed clinically by funduscopy and confirmed by histology.
  
  
  RESULTS
  Tko mice were found to have less naive, but more activated, memory T cells, among which were exhibited high sensitivity to ocular IRBP autoantigens. Immunization with a low dose of IRBP and adoptive transfer of small numbers of IRBP-specific T cells from immunized tko mice caused the infiltration of lymphocytes, including CD3(+) T cells, into the tko retina.
  
  
  CONCLUSIONS
  Mice without TAM receptor spontaneously develop IRBP-specific CD4(+) T cells and are more susceptible to retinal autoantigen immunization. This TAM knockout mouse line provides an animal model with which to study the role of antigen-presenting cells in the development of T cell-mediated uveitis.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, Kentucky 40202, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
authors.forename: Qiutang
authors.initials: Q
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Ke
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Lu
authors.forename: Lixia
authors.initials: L
authors.lastname: Han
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Kaplan
authors.forename: Hui
authors.initials: H
authors.lastname: Shao
authors.forename: Qingxian
authors.initials: Q
authors.lastname: Lu
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000276:immunology*; D005136:Eye Proteins / Q000276:immunology; D005260:Female; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D012160:Retina / Q000276:immunology* / Q000473:pathology; D012164:Retinal Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012177:Retinol-Binding Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D001324:Autoantigens; D005136:Eye Proteins; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial