Geraint P Williams1, Annette Pachnio2, Heather M Long2, Saaeha Rauz1, S John Curnow1. 1. Academic Unit of Ophthalmology, Birmingham and Midland Eye Centre, City Hospital, Birmingham, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom Centre for Translational Inflammation Research, Queen Elizabeth Hospital Birmingham, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom. 2. School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
Abstract
PURPOSE: Conjunctival epithelial T cells are dominated by CD3(+)CD56-TCRαβ(+)CD8αβ(+) lymphocytes. In this study we explored the antigen experience status, mucosal homing phenotype, cytokine expression, and viral antigen recognition of conjunctival epithelial CD8(+) T cells from healthy individuals. METHODS: Following ocular surface impression cytology, conjunctival cells were recovered by gentle agitation and analyzed by flow cytometry for cell surface markers, cytokine production (stimulated by phorbol 12-myristate 13-acetate [PMA]/ionomycin), and Epstein-Barr virus (EBV)/cytomegalovirus (CMV) immunodominant epitope recognition using major histocompatibility complex (MHC) class I peptide tetramers. RESULTS: In contrast to peripheral blood, conjunctival epithelial CD8(+) T cells were dominantly CD45RA(-)CCR7(-) effector memory cells, and the vast majority expressed the mucosal homing integrin αEβ7. Conjunctival memory CD8(+) T cells maintained effector functions with the ability to secrete IFN-γ and expression of Granzyme B, although they expressed significantly reduced amounts per cell compared to peripheral blood T cells. Interestingly, herpetic virus-specific CD8(+) T cells recognizing epitopes derived from EBV and CMV could be detected in the conjunctival cells of healthy virus carriers, although they were generally at lower frequencies than in the peripheral blood of the same donor. Virus-specific conjunctival CD8(+) T cells were dominated by CD45RA(-)CCR7(-) effector memory cells that expressed αEβ7. CONCLUSIONS: These data demonstrate that the majority of conjunctival epithelial CD8(+) T cells are mucosal homing αEβ7(+) effector memory T cells, which can recognize viral epitopes and are capable of secreting Granzyme B and IFN-γ. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
PURPOSE: Conjunctival epithelial T cells are dominated by CD3(+)CD56-TCRαβ(+)CD8αβ(+) lymphocytes. In this study we explored the antigen experience status, mucosal homing phenotype, cytokine expression, and viral antigen recognition of conjunctival epithelial CD8(+) T cells from healthy individuals. METHODS: Following ocular surface impression cytology, conjunctival cells were recovered by gentle agitation and analyzed by flow cytometry for cell surface markers, cytokine production (stimulated by phorbol 12-myristate 13-acetate [PMA]/ionomycin), and Epstein-Barr virus (EBV)/cytomegalovirus (CMV) immunodominant epitope recognition using major histocompatibility complex (MHC) class I peptide tetramers. RESULTS: In contrast to peripheral blood, conjunctival epithelial CD8(+) T cells were dominantly CD45RA(-)CCR7(-) effector memory cells, and the vast majority expressed the mucosal homing integrin αEβ7. Conjunctival memoryCD8(+) T cells maintained effector functions with the ability to secrete IFN-γ and expression of Granzyme B, although they expressed significantly reduced amounts per cell compared to peripheral blood T cells. Interestingly, herpetic virus-specific CD8(+) T cells recognizing epitopes derived from EBV and CMV could be detected in the conjunctival cells of healthy virus carriers, although they were generally at lower frequencies than in the peripheral blood of the same donor. Virus-specific conjunctival CD8(+) T cells were dominated by CD45RA(-)CCR7(-) effector memory cells that expressed αEβ7. CONCLUSIONS: These data demonstrate that the majority of conjunctival epithelial CD8(+) T cells are mucosal homing αEβ7(+) effector memory T cells, which can recognize viral epitopes and are capable of secreting Granzyme B and IFN-γ. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
Entities:
Keywords:
CD8+ T cell; conjunctiva; impression cytology; infection
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