T cell communication in kidney transplantation

The findings described in this thesis provide new perspectives in the mechanisms by which T follicular helper (Tfh) cells and tissue-resident memory T (TRM) cells modulate an alloimmune response after kidney transplantation. Both cell types have an effector memory phenotype and are able to mount an alloreactive response in which the function of IL-21 is involved. Moreover, these IL-21 driven T cells are active in the kidney allograft where they directly contribute to the process of rejection via the communication to CD8+ cytotoxic T cells and B cells. Furthermore, we found a broad effect of IL-21R blockade in our in vitro and in vivo transplant models all pointing to the same direction. Namely, blockade of IL-21R signaling has inhibiting effects on both the humoral and cellular arm of the alloimmune response. Overall, in this thesis we functionally characterized Tfh cells and TRM cells to gain knowledge about their role in alloreactivity after organ transplantation in patients. Our studies show that these T cell subsets communicate to other immune competent cells to enhance the alloimmune response via the formation of DSA, proinflammatory cytokines, and cytotoxins such as granzyme B and perforin. Modeling cell-to-cell communication networks of the T cells might help us to improve immunosuppressive treatment strategies, ultimately leading to enhanced kidney transplant outcomes.

• View at Worldcat

Free Full Text ( Final Version , 46mb )