| Autor: |
Ningoo, Mehek, Cruz-Encarnación, Pamela, Khilnani, Calla, Heeger, Peter S., Fribourg, Miguel |
| Zdroj: |
American journal of transplantation; 20230101, Issue: Preprints |
| Abstrakt: |
High frequencies of donor-reactive memory T cells in the periphery of transplant candidates prior to transplantation are linked to the development of post-transplant acute rejection episodes and to reduced allograft function. Rabbit anti-thymocyte globulin (rATG) effectively depletes naïve CD4+and CD8+T cells for > 6 months post-transplant, but rATG’s effects on human donor-reactive T cells have not been carefully determined. To address this, we performed T cell receptor beta chain sequencing (TCRseq) on PBMC aliquots collected pre-transplant and serially post-transplant in seven kidney transplant recipients who received rATG as induction therapy. We tracked the evolution of the donor-reactive CD4+and CD8+T cell repertoires, identified stimulated pre-transplant, CTV-(surface dye)-labeled, PBMC from each patient with donor cells or third-party cells. Our analyses showed that while rATG depleted CD4+T cells in all tested subjects, a subset of donor-reactive CD8+T cells that were present at high frequencies pre-transplant, consistent with expanded memory cells, resisted rATG depletion, underwent post-transplant expansion and were functional. Together, our data support the conclusion that a subset of human memory CD8+T cells specifically reactive to donor antigens expand in vivo despite induction therapy with rATG and thus have the potential to mediate allograft damage. |
| Databáze: |
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