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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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.
Originalsprog | Engelsk |
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Tidsskrift | Comparative Medicine |
Vol/bind | 73 |
Udgave nummer | 4 |
Sider (fra-til) | 285-293 |
ISSN | 1532-0820 |
DOI | |
Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
We thank Hanne Rosendal, Liselotte Butzkowsky Gurzulidis, Stinne Ravnsbaek, and Sara Mathez for their assistance. The work was funded by LEO A/S and the Innovation Fund, Denmark (grant number 5189-00097B).
Publisher Copyright:
© 2023 The Author(s).
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