title: Recruitment of Donor T Cells to the Eyes During Ocular GVHD in Recipients of MHC-Matched Allogeneic Hematopoietic Stem Cell Transplants.
abstract: OBJECTIVE
  The primary objective of the present study was to identify the kinetics and origin of ocular infiltrating T cells in a preclinical model of graft-versus-host disease (GVHD) that induces eye tissue damage.
  
  
  METHODS
  Graft-versus-host disease was induced using an major histocompatibility complex (MHC)-matched, minor histocompatibility-mismatched hematopoietic stem cell transplant (HSCT) model. This approach, which utilized congenic and EGFP-labeled donor populations, mimics a matched, clinically unrelated donor (MUD) cell transplant. Systemic and ocular GVHD were assessed at varying time points using clinical examination, intravital microscopy, immune phenotype via flow cytometric analyses, and immunohistochemical staining.
  
  
  RESULTS
  Following transplant, we observed characteristic changes in GVHD-associated immune phenotype as well as clinical signs present in recipients post transplant. Notably, the kinetics of the systemic changes and the ocular damage paralleled what is observed clinically, including damage to the cornea as well as the conjunctiva and lacrimal gland. Importantly, the infiltrate contained predominantly donor CD4 as well as CD8 T cells with an activated phenotype and macrophages together with effector cytokines consistent with the presence of a TH1 alloreactive population.
  
  
  CONCLUSIONS
  Overall, the findings here unequivocally demonstrated that donor T cells compose part of the corneal and ocular adnexa infiltrate in animals undergoing ocular GVHD. In total, the results describe a novel and promising preclinical model characterized by both systemic and ocular changes as detected in significant numbers of patients undergoing GVHD following allo-HSCT, which can help facilitate dissecting the underlying immune mechanisms leading to damage associated with ocular GVHD.
authors: Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States.
authors: Samantha
authors: S
authors: Herretes
authors: Department of Microbiology and Immunology, University of Miami Miller School of Medicine Sylvester Comprehensive Cancer Center, Miami, Florida, United States.
authors: Duncan B
authors: DB
authors: Ross
authors: Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States.
authors: Stephanie
authors: S
authors: Duffort
authors: Department of Microbiology and Immunology, University of Miami Miller School of Medicine Sylvester Comprehensive Cancer Center, Miami, Florida, United States.
authors: Henry
authors: H
authors: Barreras
authors: Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States.
authors: Tan
authors: T
authors: Yaohong
authors: Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States.
authors: Ali M
authors: AM
authors: Saeed
authors: Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States.
authors: Juan C
authors: JC
authors: Murillo
authors: Adult Stem Cell Transplant Program, University of Miami Miller School of Medicine Sylvester Comprehensive Cancer Center, Miami, Florida, United States 4Department of Medicine, University of Miami Miller School of Medicine Sylvester Comprehensive Cancer Ce.
authors: Krishna V
authors: KV
authors: Komanduri
authors: Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States 2Department of Microbiology and Immunology, University of Miami Miller School of Medicine Sylvester Comprehensive Cancer Center, Miami, Florida, Unit.
authors: Robert B
authors: RB
authors: Levy
authors: Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, United States 2Department of Microbiology and Immunology, University of Miami Miller School of Medicine Sylvester Comprehensive Cancer Center, Miami, Florida, Unit.
authors: Victor L
authors: VL
authors: Perez
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005128:Eye Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000637:transplantation*; D014184:Transplantation, Homologous
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