Recruitment of donor T cells to the eyes during ocular GVHD in recipients of MHC-matched allogeneic hematopoietic stem cell transplants

Samantha Herretes, Duncan B. Ross, Stephanie Duffort, Henry Barreras, Tan Yaohong, Ali M. Saeed, Juan C. Murillo, Krishna V Komanduri, Robert B Levy, Victor L Perez Quinones

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

PURPOSE. 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.

Original languageEnglish (US)
Pages (from-to)2348-2357
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume56
Issue number4
DOIs
StatePublished - 2015

Fingerprint

Graft vs Host Disease
Hematopoietic Stem Cells
Major Histocompatibility Complex
Tissue Donors
T-Lymphocytes
Transplants
Phenotype
Lacrimal Apparatus
Unrelated Donors
Histocompatibility
Conjunctiva
Cornea
Population
Macrophages
Staining and Labeling
Cytokines

Keywords

  • Allogeneic hematopoietic stem cell transplant
  • Ocular GVHD
  • T-cell infiltrates

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Recruitment of donor T cells to the eyes during ocular GVHD in recipients of MHC-matched allogeneic hematopoietic stem cell transplants. / Herretes, Samantha; Ross, Duncan B.; Duffort, Stephanie; Barreras, Henry; Yaohong, Tan; Saeed, Ali M.; Murillo, Juan C.; Komanduri, Krishna V; Levy, Robert B; Perez Quinones, Victor L.

In: Investigative Ophthalmology and Visual Science, Vol. 56, No. 4, 2015, p. 2348-2357.

Research output: Contribution to journalArticle

Herretes, Samantha ; Ross, Duncan B. ; Duffort, Stephanie ; Barreras, Henry ; Yaohong, Tan ; Saeed, Ali M. ; Murillo, Juan C. ; Komanduri, Krishna V ; Levy, Robert B ; Perez Quinones, Victor L. / Recruitment of donor T cells to the eyes during ocular GVHD in recipients of MHC-matched allogeneic hematopoietic stem cell transplants. In: Investigative Ophthalmology and Visual Science. 2015 ; Vol. 56, No. 4. pp. 2348-2357.
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T1 - Recruitment of donor T cells to the eyes during ocular GVHD in recipients of MHC-matched allogeneic hematopoietic stem cell transplants

AU - Herretes, Samantha

AU - Ross, Duncan B.

AU - Duffort, Stephanie

AU - Barreras, Henry

AU - Yaohong, Tan

AU - Saeed, Ali M.

AU - Murillo, Juan C.

AU - Komanduri, Krishna V

AU - Levy, Robert B

AU - Perez Quinones, Victor L

PY - 2015

Y1 - 2015

N2 - PURPOSE. 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.

AB - PURPOSE. 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.

KW - Allogeneic hematopoietic stem cell transplant

KW - Ocular GVHD

KW - T-cell infiltrates

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