Multiple Natural and Experimental Inflammatory Rabbit Lacrimal Gland Phenotypes

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• 作者：Austin K. Mircheff ; PhD¹ ; ² ; ^{amirchef@usc.edu" class="auth_mail" title="E-mail the corresponding author} ; Yanru Wang ; MD ; PhD¹ ; Joel E. Schechter ; MD³ ; Meng Li ; MS⁴ ; Warren Tong ; PharmD ; MS⁵ ; Mayssa Attar ; PhD⁵ ; Murty Chengalvala ; PhD⁶ ; Joe Harmuth ; BS⁶ ; Jeffery J. Prusakiewicz ; PhD⁷
• 关键词：acinar cells ; autoantigens ; dacryoadenitis ; dendritic cells ; dry eye ; keratoconjunctivitis ; Sj&ouml ; gren disease
• 刊名：The Ocular Surface
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：14
• 期：4
• 页码：460-483.e3
• 全文大小：8613 K

文摘

To investigate lacrimal gland (LG) immunophysiological and immune-mediated inflammatory process (IMIP) phenotype diversity.

Methods

Ex vivo matured dendritic cells (mDC) were loaded with acinar cell microparticles (M_P). 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 (P_i). 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-I_A) 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).

Results

Immunizing P_i dose 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 I_A scores.

Conclusions

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.