PURPOSE: Dry eye disease (DED) is associated with ocular surface inflammation that is thought to be mediated primarily by CD4 T cells. The purpose of this study was to investigate whether this T cell-mediated immune response is generated in the lymphoid compartment and to characterize the functional phenotype of the T cells activated in DED. METHODS: DED was induced in female C57BL/6 mice by exposure to a desiccating environment in the controlled environment chamber and to systemic scopolamine. T cells from regional draining lymph nodes (LNs) of DED mice and normally sighted mice were analyzed for surface activation markers (CD69 and CD154), chemokine and cytokine receptors, and proliferation potential. RESULTS: Draining LNs of DED mice showed increased frequencies of CD69- and CD154-expressing T cells with higher proliferative capacity. In addition, these LN T cells primarily showed a helper T-cell (Th)1 phenotype, expressing significantly higher levels of IFN-gamma and IL-12Rbeta2 but not IL-4R. Similarly, the LNs of DED mice showed significantly increased frequencies of T cells expressing CXCR3 and CCR5, but not CCR4, suggesting a bias toward a Th1 phenotype. CONCLUSIONS: These data demonstrate that a Th1-type immune response is induced in the regional LNs of DED mice. The identification of specific cytokine/chemokine receptors overexpressed by these T cells may signify potential novel targets/strategies for the treatment of DED.
PURPOSE:Dry eye disease (DED) is associated with ocular surface inflammation that is thought to be mediated primarily by CD4 T cells. The purpose of this study was to investigate whether this T cell-mediated immune response is generated in the lymphoid compartment and to characterize the functional phenotype of the T cells activated in DED. METHODS: DED was induced in female C57BL/6 mice by exposure to a desiccating environment in the controlled environment chamber and to systemic scopolamine. T cells from regional draining lymph nodes (LNs) of DED mice and normally sighted mice were analyzed for surface activation markers (CD69 and CD154), chemokine and cytokine receptors, and proliferation potential. RESULTS: Draining LNs of DED mice showed increased frequencies of CD69- and CD154-expressing T cells with higher proliferative capacity. In addition, these LN T cells primarily showed a helper T-cell (Th)1 phenotype, expressing significantly higher levels of IFN-gamma and IL-12Rbeta2 but not IL-4R. Similarly, the LNs of DED mice showed significantly increased frequencies of T cells expressing CXCR3 and CCR5, but not CCR4, suggesting a bias toward a Th1 phenotype. CONCLUSIONS: These data demonstrate that a Th1-type immune response is induced in the regional LNs of DED mice. The identification of specific cytokine/chemokine receptors overexpressed by these T cells may signify potential novel targets/strategies for the treatment of DED.
Authors: Michael E Stern; Jianping Gao; Tammy A Schwalb; Mylinh Ngo; David D Tieu; Chi-Chao Chan; Brenda L Reis; Scott M Whitcup; Darby Thompson; Janine A Smith Journal: Invest Ophthalmol Vis Sci Date: 2002-08 Impact factor: 4.799
Authors: Lu Chen; Pedram Hamrah; Claus Cursiefen; Qiang Zhang; Bronislaw Pytowski; J Wayne Streilein; M Reza Dana Journal: Nat Med Date: 2004-07-04 Impact factor: 53.440
Authors: Cintia S De Paiva; Arturo L Villarreal; Rosa M Corrales; Hassan T Rahman; Victor Y Chang; William J Farley; Michael E Stern; Jerry Y Niederkorn; De-Quan Li; Stephen C Pflugfelder Journal: Invest Ophthalmol Vis Sci Date: 2007-06 Impact factor: 4.799
Authors: William Foulsham; Thomas H Dohlman; Sharad K Mittal; Yukako Taketani; Rohan Bir Singh; Sharmila Masli; Reza Dana Journal: Ocul Surf Date: 2019-06-05 Impact factor: 5.033