Effect of Systemic Administration of CD4+ T cells and Local Administration of T-cell Stimulants on T-cell Activity in Psoriatic Skin Xenografts on NOG Mice
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Effect of Systemic Administration of CD4+ T cells and Local Administration of T-cell Stimulants on T-cell Activity in Psoriatic Skin Xenografts on NOG Mice. / Christensen, Pernille KF; Hansen, Axel K; Skov, Søren; Larsen, Jesper; Høyer-Hansen, Maria H; Koch, Janne.
I: Comparative Medicine, Bind 73, Nr. 4, 2023, s. 285-293.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Effect of Systemic Administration of CD4+ T cells and Local Administration of T-cell Stimulants on T-cell Activity in Psoriatic Skin Xenografts on NOG Mice
AU - Christensen, Pernille KF
AU - Hansen, Axel K
AU - Skov, Søren
AU - Larsen, Jesper
AU - Høyer-Hansen, Maria H
AU - Koch, Janne
N1 - Publisher Copyright: © 2023 The Author(s).
PY - 2023
Y1 - 2023
N2 - Immunodeficient mice engrafted with psoriatic human skin are widely used for the preclinical evaluation of new drug candidates. However, the T-cell activity, including the IL23/IL17 pathway, declines in the graft over time after engraftment, which likely affects the study data. Here, we investigated whether the T-cell activity could be sustained in xenografted psoriatic skin by local stimulation of T cells or systemic injection of autologous CD4+ T cells. We surgically transplanted human psoriatic skin from 5 untreated patients onto female NOG mice. Six days after surgery, mice received an intraperitoneal injection of autologous human CD4+ T cells, a subcutaneous injection under the grafts of a T-cell stimulation cocktail consisting of recombinant human IL2, human IL23, antihuman CD3, and antihuman CD28, or saline. Mice were euthanized 21 d after surgery and spleens and graft biopsies were collected for analysis. Human T cells were present in the grafts, and 60% of the grafts maintained the psoriatic phenotype. However, neither local T-cell stimulation nor systemic injection of autologous CD4+ T cells affected the protein levels of human IL17A, IL22, IFNγ, and TNFα in the grafts. In conclusion, NOG mice seem to accept psoriatic skin grafts, but the 2 approaches studied here did not affect human T-cell activity in the grafts. Therefore, NOG mice do not appear in this regard to be superior to other immunodeficient mice used for psoriasis xenografts.
AB - Immunodeficient mice engrafted with psoriatic human skin are widely used for the preclinical evaluation of new drug candidates. However, the T-cell activity, including the IL23/IL17 pathway, declines in the graft over time after engraftment, which likely affects the study data. Here, we investigated whether the T-cell activity could be sustained in xenografted psoriatic skin by local stimulation of T cells or systemic injection of autologous CD4+ T cells. We surgically transplanted human psoriatic skin from 5 untreated patients onto female NOG mice. Six days after surgery, mice received an intraperitoneal injection of autologous human CD4+ T cells, a subcutaneous injection under the grafts of a T-cell stimulation cocktail consisting of recombinant human IL2, human IL23, antihuman CD3, and antihuman CD28, or saline. Mice were euthanized 21 d after surgery and spleens and graft biopsies were collected for analysis. Human T cells were present in the grafts, and 60% of the grafts maintained the psoriatic phenotype. However, neither local T-cell stimulation nor systemic injection of autologous CD4+ T cells affected the protein levels of human IL17A, IL22, IFNγ, and TNFα in the grafts. In conclusion, NOG mice seem to accept psoriatic skin grafts, but the 2 approaches studied here did not affect human T-cell activity in the grafts. Therefore, NOG mice do not appear in this regard to be superior to other immunodeficient mice used for psoriasis xenografts.
U2 - 10.30802/AALAS-CM-23-000006
DO - 10.30802/AALAS-CM-23-000006
M3 - Journal article
C2 - 37625901
AN - SCOPUS:85173575218
VL - 73
SP - 285
EP - 293
JO - Comparative Medicine
JF - Comparative Medicine
SN - 1532-0820
IS - 4
ER -
ID: 389963723