• Hami Ashraf, Farid Kosari, Amir Arsalan Khorsand, Samad Muhammadnejad, Vahid Mansouri, Ahad Muhammadnejad, Naser Ahmadbeigi, and Seyed Mostafa Monzavi.
• Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
• Arch Iran Med. 2024 Dec 1; 27 (12): 683692683-692.

BackgroundXenogeneic graft-versus-host disease (xGvHD) is an inevitable confounder of preclinical evaluation of adoptive immunotherapies on tumor-bearing immunodeficient mouse models. This study was designed to appraise the clinical and histopathological effects caused by xGvHD in severely immunodeficient mice considering the T cell dosage.MethodsFifty NOG mice underwent intraperitoneal injection of three different doses of human-derived total T cells, a high dose of CD8+T cells, or vehicle (as control). Clinical and histopathological status of the study subjects were evaluated and compared according to scoring systems.ResultsIn mice receiving higher doses of total T cells, the clinical severity of xGvHD was greater. However, recipients of CD8+T cells developed none to mild xGvHD manifestations. Higher doses of T cells were associated with poorer outcomes including premature death and more severe histopathologic damages. Greater CD3+T cell tissue engraftment (immunohistochemical CD3 positivity) was associated with more severe xGvHD-induced histopathological damages. Clinical xGvHD scores were significantly correlated with histopathological xGvHD scores in total and in each tissue. Mice with severe cutaneous symptoms had higher scores of xGvHD-induced histopathologic changes in the skin. Lethargy was associated with higher histopathological scores in the lungs, liver and spleen.ConclusionIn preclinical evaluations, lower doses of T cell-based therapies are associated with milder xGvHD. Development of xGvHD may be averted by the use of CD4+T cell-depleted grafts. Histopathological and clinical scoring systems for evaluating xGvHD are significantly correlated. The lungs and liver are reliable organs for histopathological assessment and scoring of xGvHD.© 2024 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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