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Human peripheral blood CD4 T cell-engrafted non-obese diabetic-scid IL2rγ(null) H2-Ab1 (tm1Gru) Tg (human leucocyte antigen D-related 4) mice: a mouse model of human allogeneic graft-versus-host disease.
Clin Exp Immunol. 2011 Nov; 166(2):269-80.CE

Abstract

Graft-versus-host disease (GVHD) is a life-threatening complication of human allogeneic haematopoietic stem cell transplantation. Non-obese diabetic (NOD)-scid IL2rγ(null) (NSG) mice injected with human peripheral blood mononuclear cells (PBMC) engraft at high levels and develop a robust xenogeneic (xeno)-GVHD, which reproduces many aspects of the clinical disease. Here we show that enriched and purified human CD4 T cells engraft readily in NSG mice and mediate xeno-GVHD, although with slower kinetics compared to injection of whole PBMC. Moreover, purified human CD4 T cells engraft but do not induce a GVHD in NSG mice that lack murine MHC class II (NSG-H2-Ab1(tm1Gru), NSG-Ab°), demonstrating the importance of murine major histocompatibility complex (MHC) class II in the CD4-mediated xeno-response. Injection of purified human CD4 T cells from a DR4-negative donor into a newly developed NSG mouse strain that expresses human leucocyte antigen D-related 4 (HLA-DR4) but not murine class II (NSG-Ab° DR4) induces an allogeneic GVHD characterized by weight loss, fur loss, infiltration of human cells in skin, lung and liver and a high level of mortality. The ability of human CD4 T cells to mediate an allo-GVHD in NSG-Ab° DR4 mice suggests that this model will be useful to investigate acute allo-GVHD pathogenesis and to evaluate human specific therapies.

Authors+Show Affiliations

University of Massachusetts Medical School, Worcester, MA 01605, USA.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, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21985373

Citation

Covassin, L, et al. "Human Peripheral Blood CD4 T Cell-engrafted Non-obese Diabetic-scid IL2rγ(null) H2-Ab1 (tm1Gru) Tg (human Leucocyte Antigen D-related 4) Mice: a Mouse Model of Human Allogeneic Graft-versus-host Disease." Clinical and Experimental Immunology, vol. 166, no. 2, 2011, pp. 269-80.
Covassin L, Laning J, Abdi R, et al. Human peripheral blood CD4 T cell-engrafted non-obese diabetic-scid IL2rγ(null) H2-Ab1 (tm1Gru) Tg (human leucocyte antigen D-related 4) mice: a mouse model of human allogeneic graft-versus-host disease. Clin Exp Immunol. 2011;166(2):269-80.
Covassin, L., Laning, J., Abdi, R., Langevin, D. L., Phillips, N. E., Shultz, L. D., & Brehm, M. A. (2011). Human peripheral blood CD4 T cell-engrafted non-obese diabetic-scid IL2rγ(null) H2-Ab1 (tm1Gru) Tg (human leucocyte antigen D-related 4) mice: a mouse model of human allogeneic graft-versus-host disease. Clinical and Experimental Immunology, 166(2), 269-80. https://doi.org/10.1111/j.1365-2249.2011.04462.x
Covassin L, et al. Human Peripheral Blood CD4 T Cell-engrafted Non-obese Diabetic-scid IL2rγ(null) H2-Ab1 (tm1Gru) Tg (human Leucocyte Antigen D-related 4) Mice: a Mouse Model of Human Allogeneic Graft-versus-host Disease. Clin Exp Immunol. 2011;166(2):269-80. PubMed PMID: 21985373.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human peripheral blood CD4 T cell-engrafted non-obese diabetic-scid IL2rγ(null) H2-Ab1 (tm1Gru) Tg (human leucocyte antigen D-related 4) mice: a mouse model of human allogeneic graft-versus-host disease. AU - Covassin,L, AU - Laning,J, AU - Abdi,R, AU - Langevin,D L, AU - Phillips,N E, AU - Shultz,L D, AU - Brehm,M A, PY - 2011/10/12/entrez PY - 2011/10/12/pubmed PY - 2011/12/13/medline SP - 269 EP - 80 JF - Clinical and experimental immunology JO - Clin. Exp. Immunol. VL - 166 IS - 2 N2 - Graft-versus-host disease (GVHD) is a life-threatening complication of human allogeneic haematopoietic stem cell transplantation. Non-obese diabetic (NOD)-scid IL2rγ(null) (NSG) mice injected with human peripheral blood mononuclear cells (PBMC) engraft at high levels and develop a robust xenogeneic (xeno)-GVHD, which reproduces many aspects of the clinical disease. Here we show that enriched and purified human CD4 T cells engraft readily in NSG mice and mediate xeno-GVHD, although with slower kinetics compared to injection of whole PBMC. Moreover, purified human CD4 T cells engraft but do not induce a GVHD in NSG mice that lack murine MHC class II (NSG-H2-Ab1(tm1Gru), NSG-Ab°), demonstrating the importance of murine major histocompatibility complex (MHC) class II in the CD4-mediated xeno-response. Injection of purified human CD4 T cells from a DR4-negative donor into a newly developed NSG mouse strain that expresses human leucocyte antigen D-related 4 (HLA-DR4) but not murine class II (NSG-Ab° DR4) induces an allogeneic GVHD characterized by weight loss, fur loss, infiltration of human cells in skin, lung and liver and a high level of mortality. The ability of human CD4 T cells to mediate an allo-GVHD in NSG-Ab° DR4 mice suggests that this model will be useful to investigate acute allo-GVHD pathogenesis and to evaluate human specific therapies. SN - 1365-2249 UR - https://www.unboundmedicine.com/medline/citation/21985373/Human_peripheral_blood_CD4_T_cell_engrafted_non_obese_diabetic_scid_IL2rγ_null__H2_Ab1__tm1Gru__Tg__human_leucocyte_antigen_D_related_4__mice:_a_mouse_model_of_human_allogeneic_graft_versus_host_disease_ L2 - https://doi.org/10.1111/j.1365-2249.2011.04462.x DB - PRIME DP - Unbound Medicine ER -