الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 119 |  |  |
| | | from | 119 | | |
Abstract
T follicular helper cells facilitate B-cell activation, somatic hypermutation, affinity maturation, class switch recombination, and differentiation of B cells into memory B cells and plasma cells. An effector subset of CD4+ regulatory T cells called follicular regulatory T cells, that expresses CXCR5, ICOS, Bcl6, PD-1, and has high surface expression of Foxp3. T follicular regulatory cells have been identified to migrate to the B cell follicle and inhibit antibody production. The ratio of Tfh cells to TFR cells can be used to functionally predict the magnitude of antibody responses in a wide range of disease states in mice and humans. The frequency and phenotype of T follicular helper (Tfh) and T follicular regulatory (Tfr) cells are altered in the setting of kidney transplantation, particularly in patients who develop AbMR. However, the roles of Tfh and Tfr cells in AbMR after solid organ transplantation are unclear.
We developed mouse models to inducibly and potently perturb T follicular helper and T follicular regulatory cells to assess the roles of these cells in the development of DSA and AbMR. We found that Tfh cells are required for both de novo DSA responses and augmentation of DSA following pre-sensitization.
Utilizing orthotopic allogeneic kidney transplantation models, we found that deletion of T follicular helper cells at the time of transplantation resulted in less severe transplant rejection. Furthermore, using inducible T follicular regulatory cell deletion strategies, we found that T follicular regulatory cells inhibit de novo DSA formation but only have a minor role in controlling kidney transplant rejection. These studies demonstrate that T follicular helper cells promote, whereas T follicular regulatory cells inhibit, DSA to control rejection after kidney transplantation.