Abstract
Anti-human T lymphocyte porcine immunoglobulin (P-ATG) is a type of anti-thymocyte globulin (ATG) drug that has been used as an immunosuppressant for severe aplastic anemia and graft-versus-host disease for decades. However, the potential application of ATG for the direct treatment of Multiple sclerosis (MS) and the immune regulatory mechanisms are still unclear. In this study, the therapeutic effects and possible underlying mechanisms of P-ATG were evaluated in the rat model of experimental autoimmune encephalomyelitis (EAE), the animal model of MS. P-ATG could bind to T cells in both human and rat PBMCs in vitro and inhibit inflammatory cytokines secretion from stimulated T cells. P-ATG treatment effectively ameliorated behavioral and pathological alterations in EAE rats through reducing inflammatory infiltration and demyelination in the spinal cords. Moreover, P-ATG treatment significantly suppressed the immune response of T cells, as indicated by a decrease in the IFN-γ+ Th1 cell and IL-17+ Th17 cell proportions. These findings demonstrated that P-ATG attenuated EAE in rats by inhibiting the activation of helper T lymphocytes from naive T cells to Th1 and Th17 subsets. The therapeutic effect of P-ATG on EAE was independent of T lymphocyte depletion.
Acknowledgements
We would like to thank Ying Zhou, Weihuang Liu, and Yun Wei (Research Center for Medicine and Structural Biology, Wuhan University) for excellent technical support of confocal microscope, flow cytometry, and transmission electron microscopy.
Funding
This work was supported by the Natural Science Foundation of China (82171451), the National Science Foundation of Hubei Province of China (2017CFA017, 2017CFB698), the Wuhan Science and Technology Project (2019020701011444), the Dawn Project of Wuhan (Grant No.2022020801020489), the Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University (ZNLH201909), and the Medical Science Advancement Program of Wuhan University (TFJC2018001, TFLC2018001).
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Human studies: The study protocol involving human samples was approved by the Medical Ethics Committee of Zhongnan Hospital of Wuhan University (Approval No. 2022033 K). All experiments were performed in accordance with the Declaration of Helsinki and relevant institutional guidelines and regulations. Informed consent was obtained from all subjects and/or their legal guardians prior to participation in this study.
Animal studies: All animal experimental procedures were approved by Institutional Animal Care and Use Committee of Wuhan University and is reported in accordance with ARRIVE guidelines.
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Liu, J., Nie, X., Yang, F. et al. Anti-human T lymphocyte porcine immunoglobulin attenuates experimental autoimmune encephalomyelitis by inhibiting T cell activation. Sci Rep (2026). https://doi.org/10.1038/s41598-026-55508-7
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DOI: https://doi.org/10.1038/s41598-026-55508-7
