Unlike sensitized Th1 or Th17 cells, adoptively transferred sensitized Th9 cells selectively migrate to the conjunctiva, an allergy-prone tissue

Authors

• C Tan
• WS Wandu
• SJH Hinshaw
• C Chan
• I Gery

Abstract

Purpose: Conjunctiva is a membrane outside the eyeball and allergic reaction in this tissue (Conjunctivitis) is a major eye disease in humans. IL-9 and Th9 cells play pivotal roles in allergic reactions. Here, we compared the migration patterns of sensitized Th9, Th1 and Th17 when adoptively transferred into recipient mice expressing the target antigen inside the eyeball. Methods: Naïve CD4 cells transgenically expressing T-cell receptor specific to hen egg lysozyme (HEL) were activated/polarized toward Th1, Th9, or Th17 phenotypes and adoptively transferred (5 million/mouse) into syngeneic recipient mice that transgenically express HEL in their lens. Eyes collected at different time points post injection were examined histologically for inflammatory changes. RNA extracts from the recipients’ conjunctiva were analyzed by nCounter gene expression analysis (Nanostring Technologies) for changes in expression immunology-related genes. Results: Mice recipients of Th1 or Th17 developed severe intraocular changes, but essentially no changes in their conjunctivas. In contrast, Th9 cells induced minimal intraocular changes, but intense inflammation in the recipients’ conjunctivas. The conjunctival infiltrate in affected Th9 recipients comprised of a large proportion of eosinophils, the hallmark cells of allergic responses. In addition, Nanostring microarray analysis of conjunctival RNA samples revealed striking differences between Th9 and Th1 or Th17 recipients and thus identified inflammation-related genes that undergo significant expression changes in the inflamed conjunctivas. Conclusions: Th9 cells differ from Th1 and Th17 cells by selectively migrating to the conjunctiva, where they mediate an allergic process.

Scientific Focus Area: Immunology

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