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Long-term human CD34+ stem cell-engrafted nonobese diabetic/SCID/IL-2R gamma(null) mice show impaired CD8+ T cell maintenance and a functional arrest of immature NK cells

Standard

Long-term human CD34+ stem cell-engrafted nonobese diabetic/SCID/IL-2R gamma(null) mice show impaired CD8+ T cell maintenance and a functional arrest of immature NK cells. / André, Maya C; Erbacher, Annika; Gille, Christian; Schmauke, Vanessa; Goecke, Barbara; Hohberger, Alexander; Mang, Philippa; Wilhelm, Ayline; Müller, Ingo; Herr, Wolfgang; Lang, Peter; Handgretinger, Rupert; Hartwig, Udo F.

in: J IMMUNOL, Jahrgang 185, Nr. 5, 01.09.2010, S. 2710-20.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

André, MC, Erbacher, A, Gille, C, Schmauke, V, Goecke, B, Hohberger, A, Mang, P, Wilhelm, A, Müller, I, Herr, W, Lang, P, Handgretinger, R & Hartwig, UF 2010, 'Long-term human CD34+ stem cell-engrafted nonobese diabetic/SCID/IL-2R gamma(null) mice show impaired CD8+ T cell maintenance and a functional arrest of immature NK cells', J IMMUNOL, Jg. 185, Nr. 5, S. 2710-20. https://doi.org/10.4049/jimmunol.1000583

APA

André, M. C., Erbacher, A., Gille, C., Schmauke, V., Goecke, B., Hohberger, A., Mang, P., Wilhelm, A., Müller, I., Herr, W., Lang, P., Handgretinger, R., & Hartwig, U. F. (2010). Long-term human CD34+ stem cell-engrafted nonobese diabetic/SCID/IL-2R gamma(null) mice show impaired CD8+ T cell maintenance and a functional arrest of immature NK cells. J IMMUNOL, 185(5), 2710-20. https://doi.org/10.4049/jimmunol.1000583

Vancouver

André MC, Erbacher A, Gille C, Schmauke V, Goecke B, Hohberger A et al. Long-term human CD34+ stem cell-engrafted nonobese diabetic/SCID/IL-2R gamma(null) mice show impaired CD8+ T cell maintenance and a functional arrest of immature NK cells. J IMMUNOL. 2010 Sep 1;185(5):2710-20. https://doi.org/10.4049/jimmunol.1000583

Bibtex

@article{63c82e32e8414fc18ba548fb9ab47945,
title = "Long-term human CD34+ stem cell-engrafted nonobese diabetic/SCID/IL-2R gamma(null) mice show impaired CD8+ T cell maintenance and a functional arrest of immature NK cells",
abstract = "Allogeneic hematopoietic stem cell transplantation represents the most effective form of immunotherapy for chemorefractory diseases. However, animal models have been missing that allow evaluation of donor-patient-specific graft-versus-leukemia effects. Thus, we sought to establish a patient-tailored humanized mouse model that would result in long-term engraftment of various lymphocytic lineages and would serve as a donor-specific surrogate. Following transfer of donor-derived peripheral blood stem cells into NOD/SCID/IL-2Rgamma(null) (NSG) mice with supplementation of human IL-7, we could demonstrate robust engraftment and multilineage differentiation comparable to earlier studies using cord blood stem cells. Phenotypical and functional analyses of lymphoid lineages revealed that >20 wk posthematopoietic stem cell transplantation, the majority of T lymphocytes consisted of memory-type CD4(+) T cells capable of inducing specific immune functions, whereas CD8(+) T cells were only present in low numbers. Analysis of NSG-derived NK cells revealed the expression of constitutively activated CD56(bright)CD16(-) killer Ig-like receptor(negative) NK cells that exhibited functional impairments. Thus, the data presented in this study demonstrate that humanized NSG mice can be successfully used to develop a xenotransplantation model that might allow patient-tailored treatment strategies in the future, but also highlight the need to improve this model, for example, by coadministration of differentiation-promoting cytokines and induction of human MHC molecules to complement existing deficiencies in NK and CD8(+) T cell development.",
keywords = "Adult, Animals, Antigens, CD34, CD8-Positive T-Lymphocytes, Cell Death, Cell Differentiation, Cell Lineage, Graft vs Leukemia Effect, Hematopoietic Stem Cell Transplantation, Humans, Interleukin Receptor Common gamma Subunit, K562 Cells, Killer Cells, Natural, Lymphocyte Culture Test, Mixed, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, Knockout, Mice, SCID, Mice, Transgenic, Transplantation, Heterologous",
author = "Andr{\'e}, {Maya C} and Annika Erbacher and Christian Gille and Vanessa Schmauke and Barbara Goecke and Alexander Hohberger and Philippa Mang and Ayline Wilhelm and Ingo M{\"u}ller and Wolfgang Herr and Peter Lang and Rupert Handgretinger and Hartwig, {Udo F}",
year = "2010",
month = sep,
day = "1",
doi = "10.4049/jimmunol.1000583",
language = "English",
volume = "185",
pages = "2710--20",
journal = "J IMMUNOL",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "5",

}

RIS

TY - JOUR

T1 - Long-term human CD34+ stem cell-engrafted nonobese diabetic/SCID/IL-2R gamma(null) mice show impaired CD8+ T cell maintenance and a functional arrest of immature NK cells

AU - André, Maya C

AU - Erbacher, Annika

AU - Gille, Christian

AU - Schmauke, Vanessa

AU - Goecke, Barbara

AU - Hohberger, Alexander

AU - Mang, Philippa

AU - Wilhelm, Ayline

AU - Müller, Ingo

AU - Herr, Wolfgang

AU - Lang, Peter

AU - Handgretinger, Rupert

AU - Hartwig, Udo F

PY - 2010/9/1

Y1 - 2010/9/1

N2 - Allogeneic hematopoietic stem cell transplantation represents the most effective form of immunotherapy for chemorefractory diseases. However, animal models have been missing that allow evaluation of donor-patient-specific graft-versus-leukemia effects. Thus, we sought to establish a patient-tailored humanized mouse model that would result in long-term engraftment of various lymphocytic lineages and would serve as a donor-specific surrogate. Following transfer of donor-derived peripheral blood stem cells into NOD/SCID/IL-2Rgamma(null) (NSG) mice with supplementation of human IL-7, we could demonstrate robust engraftment and multilineage differentiation comparable to earlier studies using cord blood stem cells. Phenotypical and functional analyses of lymphoid lineages revealed that >20 wk posthematopoietic stem cell transplantation, the majority of T lymphocytes consisted of memory-type CD4(+) T cells capable of inducing specific immune functions, whereas CD8(+) T cells were only present in low numbers. Analysis of NSG-derived NK cells revealed the expression of constitutively activated CD56(bright)CD16(-) killer Ig-like receptor(negative) NK cells that exhibited functional impairments. Thus, the data presented in this study demonstrate that humanized NSG mice can be successfully used to develop a xenotransplantation model that might allow patient-tailored treatment strategies in the future, but also highlight the need to improve this model, for example, by coadministration of differentiation-promoting cytokines and induction of human MHC molecules to complement existing deficiencies in NK and CD8(+) T cell development.

AB - Allogeneic hematopoietic stem cell transplantation represents the most effective form of immunotherapy for chemorefractory diseases. However, animal models have been missing that allow evaluation of donor-patient-specific graft-versus-leukemia effects. Thus, we sought to establish a patient-tailored humanized mouse model that would result in long-term engraftment of various lymphocytic lineages and would serve as a donor-specific surrogate. Following transfer of donor-derived peripheral blood stem cells into NOD/SCID/IL-2Rgamma(null) (NSG) mice with supplementation of human IL-7, we could demonstrate robust engraftment and multilineage differentiation comparable to earlier studies using cord blood stem cells. Phenotypical and functional analyses of lymphoid lineages revealed that >20 wk posthematopoietic stem cell transplantation, the majority of T lymphocytes consisted of memory-type CD4(+) T cells capable of inducing specific immune functions, whereas CD8(+) T cells were only present in low numbers. Analysis of NSG-derived NK cells revealed the expression of constitutively activated CD56(bright)CD16(-) killer Ig-like receptor(negative) NK cells that exhibited functional impairments. Thus, the data presented in this study demonstrate that humanized NSG mice can be successfully used to develop a xenotransplantation model that might allow patient-tailored treatment strategies in the future, but also highlight the need to improve this model, for example, by coadministration of differentiation-promoting cytokines and induction of human MHC molecules to complement existing deficiencies in NK and CD8(+) T cell development.

KW - Adult

KW - Animals

KW - Antigens, CD34

KW - CD8-Positive T-Lymphocytes

KW - Cell Death

KW - Cell Differentiation

KW - Cell Lineage

KW - Graft vs Leukemia Effect

KW - Hematopoietic Stem Cell Transplantation

KW - Humans

KW - Interleukin Receptor Common gamma Subunit

KW - K562 Cells

KW - Killer Cells, Natural

KW - Lymphocyte Culture Test, Mixed

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Inbred C57BL

KW - Mice, Inbred NOD

KW - Mice, Knockout

KW - Mice, SCID

KW - Mice, Transgenic

KW - Transplantation, Heterologous

U2 - 10.4049/jimmunol.1000583

DO - 10.4049/jimmunol.1000583

M3 - SCORING: Journal article

C2 - 20668220

VL - 185

SP - 2710

EP - 2720

JO - J IMMUNOL

JF - J IMMUNOL

SN - 0022-1767

IS - 5

ER -