title: Multiple Natural and Experimental Inflammatory Rabbit Lacrimal Gland Phenotypes.
abstract: To investigate lacrimal gland (LG) immunophysiological and immune-mediated inflammatory process (IMIP) phenotype diversity.
  
  
  
  Ex vivo matured dendritic cells (mDC) were loaded with acinar cell microparticles (MP). Peripheral blood lymphocytes (PBL) were activated in mixed cell reactions with mDC and injected directly into autologous, unilateral LG (1°ATD-LG) of two rabbit cohorts, one naïve, one immunized with a LG lysate membrane fraction (Pi). Autoimmune IgG titers were assayed by ELISA, MCR PBL stimulation indices (SI) by [3H]-thymidine incorporation. Schirmer tests without and with topical anesthetic (STT-I, STT-IA) and rose Bengal (RB) staining tests were performed. H&E and immunohistochemically stained sections were examined. RNA yields and selected transcript abundances were measured. Immune cell number and transcript abundance data were submitted to Principal Component Analysis (PCA).
  
  
  
  Immunizing Pidose influenced SI but not IgG titers. STT scores were decreased, and rose Bengal scores increased, by day 118 after immunization. Previous immunization exacerbated scores in 1°ATD-eyes and exacerbated 1°ATD-LG atrophy. IMIP were evident in 2°ATD-LG as well as 1°ATD-LG. PCA described diverse immunophysiological phenotypes in control LG and diverse IMIP phenotypes in ATD-LG. IgG titers and SI pre-adoptive transfer were significantly associated with certain post-adoptive transfer IMIP phenotype features, and certain LG IMIP features were significantly associated with RB and STT IAscores.
  
  
  
  The underlying variability of normal states may contribute to the diversity of experimental IMIP phenotypes. The ability to generate and characterize diverse phenotypes may lead to phenotype-specific diagnostic and therapeutic paradigms.
authors.affiliation: Department of Physiology & Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: amirchef@usc.edu.
authors.forename: Austin K
authors.initials: AK
authors.lastname: Mircheff
authors.affiliation: Department of Physiology & Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Yanru
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cell & Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Joel E
authors.initials: JE
authors.lastname: Schechter
authors.affiliation: Bioinformatics Service, Norris Medical Library, University of Southern California, Los Angeles, CA, USA.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: Translational Drug Metabolism, Pharmacokinetics and Immunology, Allergan Inc., Irvine, CA, USA.
authors.forename: Warren
authors.initials: W
authors.lastname: Tong
authors.affiliation: Translational Drug Metabolism, Pharmacokinetics and Immunology, Allergan Inc., Irvine, CA, USA.
authors.forename: Mayssa
authors.initials: M
authors.lastname: Attar
authors.affiliation: Immunology Services, Covance Research Products, Denver, PA, USA.
authors.forename: Murty
authors.initials: M
authors.lastname: Chengalvala
authors.affiliation: Immunology Services, Covance Research Products, Denver, PA, USA.
authors.forename: Joe
authors.initials: J
authors.lastname: Harmuth
authors.affiliation: Drug Metabolism, Covance Laboratories Inc., Madison, WI, USA.
authors.forename: Jeffery J
authors.initials: JJ
authors.lastname: Prusakiewicz
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity; D015153:Blotting, Western; D003607:Dacryocystitis / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D016130:Immunophenotyping; D007765:Lacrimal Apparatus / Q000276:immunology*; D008213:Lymphocyte Activation; D025341:Principal Component Analysis; D011817:Rabbits; D060888:Real-Time Polymerase Chain Reaction; D012395:Rose Bengal
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D012395:Rose Bengal
keywords: Sjögren disease; acinar cells; autoantigens; dacryoadenitis; dendritic cells; dry eye; keratoconjunctivitis