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Xenogeneic graft-versus-host-disease in NOD-scid IL-2Rγnull mice display a T-effector memory phenotype.
PLoS One. 2012; 7(8):e44219.Plos

Abstract

The occurrence of Graft-versus-Host Disease (GvHD) is a prevalent and potentially lethal complication that develops following hematopoietic stem cell transplantation. Humanized mouse models of xenogeneic-GvHD based upon immunodeficient strains injected with human peripheral blood mononuclear cells (PBMC; "Hu-PBMC mice") are important tools to study human immune function in vivo. The recent introduction of targeted deletions at the interleukin-2 common gamma chain (IL-2Rγ(null)), notably the NOD-scid IL-2Rγ(null) (NSG) and BALB/c-Rag2(null) IL-2Rγ(null) (BRG) mice, has led to improved human cell engraftment. Despite their widespread use, a comprehensive characterisation of engraftment and GvHD development in the Hu-PBMC NSG and BRG models has never been performed in parallel. We compared engrafted human lymphocyte populations in the peripheral blood, spleens, lymph nodes and bone marrow of these mice. Kinetics of engraftment differed between the two strains, in particular a significantly faster expansion of the human CD45(+) compartment and higher engraftment levels of CD3(+) T-cells were observed in NSG mice, which may explain the faster rate of GvHD development in this model. The pathogenesis of human GvHD involves anti-host effector cell reactivity and cutaneous tissue infiltration. Despite this, the presence of T-cell subsets and tissue homing markers has only recently been characterised in the peripheral blood of patients and has never been properly defined in Hu-PBMC models of GvHD. Engrafted human cells in NSG mice shows a prevalence of tissue homing cells with a T-effector memory (T(EM)) phenotype and high levels of cutaneous lymphocyte antigen (CLA) expression. Characterization of Hu-PBMC mice provides a strong preclinical platform for the application of novel immunotherapies targeting T(EM)-cell driven GvHD.

Authors+Show Affiliations

St. John's Institute of Dermatology, King's College London and NIHR Biomedical Research Centre, London, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22937164

Citation

Ali, Niwa, et al. "Xenogeneic Graft-versus-host-disease in NOD-scid IL-2Rγnull Mice Display a T-effector Memory Phenotype." PloS One, vol. 7, no. 8, 2012, pp. e44219.
Ali N, Flutter B, Sanchez Rodriguez R, et al. Xenogeneic graft-versus-host-disease in NOD-scid IL-2Rγnull mice display a T-effector memory phenotype. PLoS ONE. 2012;7(8):e44219.
Ali, N., Flutter, B., Sanchez Rodriguez, R., Sharif-Paghaleh, E., Barber, L. D., Lombardi, G., & Nestle, F. O. (2012). Xenogeneic graft-versus-host-disease in NOD-scid IL-2Rγnull mice display a T-effector memory phenotype. PloS One, 7(8), e44219. https://doi.org/10.1371/journal.pone.0044219
Ali N, et al. Xenogeneic Graft-versus-host-disease in NOD-scid IL-2Rγnull Mice Display a T-effector Memory Phenotype. PLoS ONE. 2012;7(8):e44219. PubMed PMID: 22937164.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Xenogeneic graft-versus-host-disease in NOD-scid IL-2Rγnull mice display a T-effector memory phenotype. AU - Ali,Niwa, AU - Flutter,Barry, AU - Sanchez Rodriguez,Robert, AU - Sharif-Paghaleh,Ehsan, AU - Barber,Linda D, AU - Lombardi,Giovanna, AU - Nestle,Frank O, Y1 - 2012/08/28/ PY - 2012/05/27/received PY - 2012/08/03/accepted PY - 2012/9/1/entrez PY - 2012/9/1/pubmed PY - 2013/2/13/medline SP - e44219 EP - e44219 JF - PloS one JO - PLoS ONE VL - 7 IS - 8 N2 - The occurrence of Graft-versus-Host Disease (GvHD) is a prevalent and potentially lethal complication that develops following hematopoietic stem cell transplantation. Humanized mouse models of xenogeneic-GvHD based upon immunodeficient strains injected with human peripheral blood mononuclear cells (PBMC; "Hu-PBMC mice") are important tools to study human immune function in vivo. The recent introduction of targeted deletions at the interleukin-2 common gamma chain (IL-2Rγ(null)), notably the NOD-scid IL-2Rγ(null) (NSG) and BALB/c-Rag2(null) IL-2Rγ(null) (BRG) mice, has led to improved human cell engraftment. Despite their widespread use, a comprehensive characterisation of engraftment and GvHD development in the Hu-PBMC NSG and BRG models has never been performed in parallel. We compared engrafted human lymphocyte populations in the peripheral blood, spleens, lymph nodes and bone marrow of these mice. Kinetics of engraftment differed between the two strains, in particular a significantly faster expansion of the human CD45(+) compartment and higher engraftment levels of CD3(+) T-cells were observed in NSG mice, which may explain the faster rate of GvHD development in this model. The pathogenesis of human GvHD involves anti-host effector cell reactivity and cutaneous tissue infiltration. Despite this, the presence of T-cell subsets and tissue homing markers has only recently been characterised in the peripheral blood of patients and has never been properly defined in Hu-PBMC models of GvHD. Engrafted human cells in NSG mice shows a prevalence of tissue homing cells with a T-effector memory (T(EM)) phenotype and high levels of cutaneous lymphocyte antigen (CLA) expression. Characterization of Hu-PBMC mice provides a strong preclinical platform for the application of novel immunotherapies targeting T(EM)-cell driven GvHD. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/22937164/Xenogeneic_graft_versus_host_disease_in_NOD_scid_IL_2Rγnull_mice_display_a_T_effector_memory_phenotype_ L2 - http://dx.plos.org/10.1371/journal.pone.0044219 DB - PRIME DP - Unbound Medicine ER -