Quante, Markus and Heinbokel, Timm and Edtinger, Karoline and Minami, Koichiro and Uehara, Hirofumi and Nian, Yeqi and Azuma, Haruhito and Abdi, Reza and Elkhal, Abdallah and Tullius, Stefan G. (2018) Rapamycin Prolongs Graft Survival and Induces CD4(+)IFN-gamma+IL-10(+) Regulatory Type 1 Cells in Old Recipient Mice. TRANSPLANTATION, 102 (1). pp. 59-69. ISSN 0041-1337, 1534-6080
Full text not available from this repository. (Request a copy)Abstract
Background. Although the elderly represents a rapidly growing population among transplant recipients, age-specific aspects have not been considered sufficiently in clinical trials. Moreover, age-specific effects of immunosuppressive therapies remain poorly understood. Methods. Here, we assessed the impact of rapamycin on alloimmune responses in old recipients using a fully major histocompatibility complex-mismatched murine transplantation model. Results. Old untreated recipients displayed a prolonged skin graft survival compared to their young counterparts, an observation that confirmed data of our previous experiments. Rapamycin led to a significant prolongation of graft survival in both young and old recipients. However, graft survival was age-dependent and extended in old versus young recipients (19 days vs 12 days, P = 0.004). This age-specific effect was not linked to changes in frequencies or subset composition of either cluster of differentiation (CD)8(+) or CD4(+) Tcells. Moreover, antiproliferative effects of rapamycin on CD8(+) and CD4(+) T cells as assessed by in vivo bromdesoxyuridine incorporation were comparable and age-independent. In contrast, the systemic production of IL-10 was markedly elevated in old recipients treated with rapamycin. In parallel to this shift in cytokine balance, IFN-gamma/IL-10 double-positive regulatory type 1 cells emerged during T helper type 1 differentiation of old T helper cells in presence of rapamycin. Similarly, CD4(+) IFN-gamma(+) IL-10(+) cells expanded among Foxp3-negative cells after in vivo treatment of old recipients with rapamycin. Conclusions. Our results highlight novel aspects of age-dependent immunosuppressive effects of rapamycin, with relevance for age-specific immunosuppressive regimens.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | T-CELLS; KIDNEY-TRANSPLANTATION; ORGAN-TRANSPLANTATION; AGE; CD4(+); EXPANSION; TARGET; DIFFERENTIATION; TOLERANCE; REJECTION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Mar 2020 13:32 |
| Last Modified: | 20 Mar 2020 13:32 |
| URI: | https://pred.uni-regensburg.de/id/eprint/15472 |
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