PURPOSE: 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.
PURPOSE: 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: R S Scott; E J McMahon; S M Pop; E A Reap; R Caricchio; P L Cohen; H S Earp; G K Matsushima Journal: Nature Date: 2001-05-10 Impact factor: 49.962
Authors: J P O'Bryan; R A Frye; P C Cogswell; A Neubauer; B Kitch; C Prokop; R Espinosa; M M Le Beau; H S Earp; E T Liu Journal: Mol Cell Biol Date: 1991-10 Impact factor: 4.272
Authors: Nan Li; Zhenghui Liu; Yue Zhang; Qiaoyuan Chen; Peng Liu; C Yan Cheng; Will M Lee; Yongmei Chen; Daishu Han Journal: Immunol Cell Biol Date: 2014-11-18 Impact factor: 5.126
Authors: Xiu-Feng Huang; Zhixiu Li; Erika De Guzman; Philip Robinson; Lianne Gensler; Michael M Ward; Mohammad Hossein Rahbar; MinJae Lee; Michael H Weisman; Gary J Macfarlane; Gareth T Jones; Eva Klingberg; Helena Forsblad-d'Elia; Peter McCluskey; Denis Wakefield; Jeff S Coombes; Maria A Fiatarone Singh; Yorgi Mavros; Nicole Vlahovich; David C Hughes; Helena Marzo-Ortega; Irene Van der Horste-Bruinsma; Finbar O'Shea; Tammy M Martin; James Rosenbaum; Maxime Breban; Zi-Bing Jin; Paul Leo; John D Reveille; B Paul Wordsworth; Matthew A Brown Journal: Invest Ophthalmol Vis Sci Date: 2020-06-03 Impact factor: 4.799