Factors affecting human T cell engraftment, trafficking, and associated xenogeneic graft-vs-host disease in NOD/SCID β2mnull mice

Bruno Nervi, Michael P. Rettig, Julie K. Ritchey, Hanlin L. Wang, Gerhard Bauer, Jon Walker, Mark L. Bonyhadi, Ronald J. Berenson, Julie L. Prior, David Piwnica-Worms, Jan Nolta, John F. DiPersio

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Objective: Graft-vs-host disease (GVHD) is the major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Models of immunodeficient mice that consistently and efficiently reconstitute with xenoreactive human T cells would be a valuable tool for the in vivo study of GVHD, as well as other human immune responses. Materials and Methods: We developed a consistent and sensitive model of human GVHD by retro-orbitally injecting purified human T cells into sublethally irradiated nonobese diabetic/severe combined immunodeficient (NOD/SCID)-β2mnull recipients. In addition, we characterized for the first time the trafficking patterns and expansion profiles of xenoreactive human T cells in NOD/SCID-β2mnull recipients using in vivo bioluminescence imaging. Results: All NOD/SCID-β2mnull mice conditioned with 300 cGy total body irradiation and injected with 1 × 107 human T cells exhibited human T-cell engraftment, activation, and expansion, with infiltration of multiple target tissues and a subsequent >20% loss of pretransplantation body weight. Importantly, histological examination of the GVHD target tissues revealed changes consistent with human GVHD. Furthermore, we also showed by in vivo bioluminescence imaging that development of lethal GVHD in the NOD/SCID-β2mnull recipients was dependent upon the initial retention and early expansion of human T cells in the retro-orbital sinus cavity. Conclusion: Our NOD/SCID-β2mnull mouse model provides a system to study the pathophysiology of acute GVHD induced by human T cells and aids in development of more effective therapies for human GVHD.

Original languageEnglish (US)
Pages (from-to)1823-1838
Number of pages16
JournalExperimental Hematology
Volume35
Issue number12
DOIs
StatePublished - Dec 2007
Externally publishedYes

Fingerprint

SCID Mice
Graft vs Host Disease
T-Lymphocytes
Whole-Body Irradiation
Hematopoietic Stem Cell Transplantation
Body Weight
Morbidity

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

Factors affecting human T cell engraftment, trafficking, and associated xenogeneic graft-vs-host disease in NOD/SCID β2mnull mice. / Nervi, Bruno; Rettig, Michael P.; Ritchey, Julie K.; Wang, Hanlin L.; Bauer, Gerhard; Walker, Jon; Bonyhadi, Mark L.; Berenson, Ronald J.; Prior, Julie L.; Piwnica-Worms, David; Nolta, Jan; DiPersio, John F.

In: Experimental Hematology, Vol. 35, No. 12, 12.2007, p. 1823-1838.

Research output: Contribution to journalArticle

Nervi, B, Rettig, MP, Ritchey, JK, Wang, HL, Bauer, G, Walker, J, Bonyhadi, ML, Berenson, RJ, Prior, JL, Piwnica-Worms, D, Nolta, J & DiPersio, JF 2007, 'Factors affecting human T cell engraftment, trafficking, and associated xenogeneic graft-vs-host disease in NOD/SCID β2mnull mice', Experimental Hematology, vol. 35, no. 12, pp. 1823-1838. https://doi.org/10.1016/j.exphem.2007.06.007
Nervi, Bruno ; Rettig, Michael P. ; Ritchey, Julie K. ; Wang, Hanlin L. ; Bauer, Gerhard ; Walker, Jon ; Bonyhadi, Mark L. ; Berenson, Ronald J. ; Prior, Julie L. ; Piwnica-Worms, David ; Nolta, Jan ; DiPersio, John F. / Factors affecting human T cell engraftment, trafficking, and associated xenogeneic graft-vs-host disease in NOD/SCID β2mnull mice. In: Experimental Hematology. 2007 ; Vol. 35, No. 12. pp. 1823-1838.
@article{d8c5baebaf4940f0baa4d437efaaba24,
title = "Factors affecting human T cell engraftment, trafficking, and associated xenogeneic graft-vs-host disease in NOD/SCID β2mnull mice",
abstract = "Objective: Graft-vs-host disease (GVHD) is the major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Models of immunodeficient mice that consistently and efficiently reconstitute with xenoreactive human T cells would be a valuable tool for the in vivo study of GVHD, as well as other human immune responses. Materials and Methods: We developed a consistent and sensitive model of human GVHD by retro-orbitally injecting purified human T cells into sublethally irradiated nonobese diabetic/severe combined immunodeficient (NOD/SCID)-β2mnull recipients. In addition, we characterized for the first time the trafficking patterns and expansion profiles of xenoreactive human T cells in NOD/SCID-β2mnull recipients using in vivo bioluminescence imaging. Results: All NOD/SCID-β2mnull mice conditioned with 300 cGy total body irradiation and injected with 1 × 107 human T cells exhibited human T-cell engraftment, activation, and expansion, with infiltration of multiple target tissues and a subsequent >20{\%} loss of pretransplantation body weight. Importantly, histological examination of the GVHD target tissues revealed changes consistent with human GVHD. Furthermore, we also showed by in vivo bioluminescence imaging that development of lethal GVHD in the NOD/SCID-β2mnull recipients was dependent upon the initial retention and early expansion of human T cells in the retro-orbital sinus cavity. Conclusion: Our NOD/SCID-β2mnull mouse model provides a system to study the pathophysiology of acute GVHD induced by human T cells and aids in development of more effective therapies for human GVHD.",
author = "Bruno Nervi and Rettig, {Michael P.} and Ritchey, {Julie K.} and Wang, {Hanlin L.} and Gerhard Bauer and Jon Walker and Bonyhadi, {Mark L.} and Berenson, {Ronald J.} and Prior, {Julie L.} and David Piwnica-Worms and Jan Nolta and DiPersio, {John F.}",
year = "2007",
month = "12",
doi = "10.1016/j.exphem.2007.06.007",
language = "English (US)",
volume = "35",
pages = "1823--1838",
journal = "Experimental Hematology",
issn = "0301-472X",
publisher = "Elsevier Inc.",
number = "12",

}

TY - JOUR

T1 - Factors affecting human T cell engraftment, trafficking, and associated xenogeneic graft-vs-host disease in NOD/SCID β2mnull mice

AU - Nervi, Bruno

AU - Rettig, Michael P.

AU - Ritchey, Julie K.

AU - Wang, Hanlin L.

AU - Bauer, Gerhard

AU - Walker, Jon

AU - Bonyhadi, Mark L.

AU - Berenson, Ronald J.

AU - Prior, Julie L.

AU - Piwnica-Worms, David

AU - Nolta, Jan

AU - DiPersio, John F.

PY - 2007/12

Y1 - 2007/12

N2 - Objective: Graft-vs-host disease (GVHD) is the major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Models of immunodeficient mice that consistently and efficiently reconstitute with xenoreactive human T cells would be a valuable tool for the in vivo study of GVHD, as well as other human immune responses. Materials and Methods: We developed a consistent and sensitive model of human GVHD by retro-orbitally injecting purified human T cells into sublethally irradiated nonobese diabetic/severe combined immunodeficient (NOD/SCID)-β2mnull recipients. In addition, we characterized for the first time the trafficking patterns and expansion profiles of xenoreactive human T cells in NOD/SCID-β2mnull recipients using in vivo bioluminescence imaging. Results: All NOD/SCID-β2mnull mice conditioned with 300 cGy total body irradiation and injected with 1 × 107 human T cells exhibited human T-cell engraftment, activation, and expansion, with infiltration of multiple target tissues and a subsequent >20% loss of pretransplantation body weight. Importantly, histological examination of the GVHD target tissues revealed changes consistent with human GVHD. Furthermore, we also showed by in vivo bioluminescence imaging that development of lethal GVHD in the NOD/SCID-β2mnull recipients was dependent upon the initial retention and early expansion of human T cells in the retro-orbital sinus cavity. Conclusion: Our NOD/SCID-β2mnull mouse model provides a system to study the pathophysiology of acute GVHD induced by human T cells and aids in development of more effective therapies for human GVHD.

AB - Objective: Graft-vs-host disease (GVHD) is the major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Models of immunodeficient mice that consistently and efficiently reconstitute with xenoreactive human T cells would be a valuable tool for the in vivo study of GVHD, as well as other human immune responses. Materials and Methods: We developed a consistent and sensitive model of human GVHD by retro-orbitally injecting purified human T cells into sublethally irradiated nonobese diabetic/severe combined immunodeficient (NOD/SCID)-β2mnull recipients. In addition, we characterized for the first time the trafficking patterns and expansion profiles of xenoreactive human T cells in NOD/SCID-β2mnull recipients using in vivo bioluminescence imaging. Results: All NOD/SCID-β2mnull mice conditioned with 300 cGy total body irradiation and injected with 1 × 107 human T cells exhibited human T-cell engraftment, activation, and expansion, with infiltration of multiple target tissues and a subsequent >20% loss of pretransplantation body weight. Importantly, histological examination of the GVHD target tissues revealed changes consistent with human GVHD. Furthermore, we also showed by in vivo bioluminescence imaging that development of lethal GVHD in the NOD/SCID-β2mnull recipients was dependent upon the initial retention and early expansion of human T cells in the retro-orbital sinus cavity. Conclusion: Our NOD/SCID-β2mnull mouse model provides a system to study the pathophysiology of acute GVHD induced by human T cells and aids in development of more effective therapies for human GVHD.

UR - http://www.scopus.com/inward/record.url?scp=36148965120&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36148965120&partnerID=8YFLogxK

U2 - 10.1016/j.exphem.2007.06.007

DO - 10.1016/j.exphem.2007.06.007

M3 - Article

VL - 35

SP - 1823

EP - 1838

JO - Experimental Hematology

JF - Experimental Hematology

SN - 0301-472X

IS - 12

ER -