Pathogen Stimulation History Impacts Donor-Specific CD8(+) T Cell Susceptibility to Costimulation/Integrin Blockade-Based Therapy.
In: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, Jg. 15 (2015-12-01), Heft 12, S. 3081-94
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Zugriff:
Recent studies have shown that the quantity of donor-reactive memory T cells is an important factor in determining the relative heterologous immunity barrier posed during transplantation. Here, we hypothesized that the quality of T cell memory also potently influences the response to costimulation blockade-based immunosuppression. Using a murine skin graft model of CD8(+) memory T cell-mediated costimulation blockade resistance, we elicited donor-reactive memory T cells using three distinct types of pathogen infections. Strikingly, we observed differential efficacy of a costimulation and integrin blockade regimen based on the type of pathogen used to elicit the donor-reactive memory T cell response. Intriguingly, the most immunosuppression-sensitive memory T cell populations were composed primarily of central memory cells that possessed greater recall potential, exhibited a less differentiated phenotype, and contained more multi-cytokine producers. These data, therefore, demonstrate that the memory T cell barrier is dependent on the specific type of pathogen infection via which the donor-reactive memory T cells are elicited, and suggest that the immune stimulation history of a given transplant patient may profoundly influence the relative barrier posed by heterologous immunity during transplantation.
(© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)
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Pathogen Stimulation History Impacts Donor-Specific CD8(+) T Cell Susceptibility to Costimulation/Integrin Blockade-Based Therapy.
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Autor/in / Beteiligte Person: | Badell, IR ; Kitchens, WH ; Wagener, ME ; Lukacher, AE ; Larsen, CP ; Ford, ML |
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Zeitschrift: | American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, Jg. 15 (2015-12-01), Heft 12, S. 3081-94 |
Veröffentlichung: | 2023- : [New York] : Elsevier ; <i>Original Publication</i>: Copenhagen : Munksgaard International Publishers, 2001-, 2015 |
Medientyp: | academicJournal |
ISSN: | 1600-6143 (electronic) |
DOI: | 10.1111/ajt.13399 |
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