Summary:
After transplant, the immune system is reconstituted by cells derived from both hematopoietic stem cells and peripheral expansion from differentiated donor T cells. After transplant, immune function is poor despite transplantation of mature lymphocytes from immune-competent donors. We tested the hypothesis that early antigen encounter at the time of cell transplant would improve the desired donor T-cell responses. Two independent models of peptide-specific T-cell responses were studied. The model for CD4 cells employed T cells from transgenic (Tg) DO11.11 mice that constitutively express the T-cell receptor for the class II-restricted ovalbumin peptide 323–339. The model for CD8 cells employed non-Tg H2-Db-restricted T-cell responses to the influenza nucleoprotein peptide 366–374. As measured both functionally and by direct imaging of T cells using clonotypic reagents, encounter with specific antigen at the time of T-cell transplantation led to clonal expansion of donor T cells and preservation of donor T-cell function in the post transplant immune environment. Antigen-specific donor T-cell function was poor if antigen encounter was delayed or omitted. Severe parent>F1 graft-versus-host reactions blocked the effect of early antigen exposure. Vaccination of transplant recipients against microbial or leukemia antigens may be worthy of study.
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Acknowledgements
This work was supported in part by a Research Scholar Grant (RSG-98-035-04-LIB) from the American Cancer Society (CAM) and grant support from the National Institutes of Health (5T32CA073954-05) (SM) (1 R01 CA10628-01) (CAM). We are grateful to Dr Cherylyn Savary for her generous assistance with flow cytometry.
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Mori, S., Kocak, U., Shaw, J. et al. Augmentation of post transplant immunity: antigen encounter at the time of hematopoietic stem cell transplantation enhances antigen-specific donor T-cell responses in the post transplant repertoire. Bone Marrow Transplant 35, 793–801 (2005). https://doi.org/10.1038/sj.bmt.1704883
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DOI: https://doi.org/10.1038/sj.bmt.1704883
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