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Kidney Week

Abstract: FR-PO1103

B Cell and T Cell Subset Changes in a Rat Kidney Transplant Model of Chronic Antibody-Mediated Rejection

Session Information

  • Transplantation: Basic
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

  • 1901 Transplantation: Basic

Authors

  • Wilson, Nancy A., University of Wisconsin Madison, Madison, Wisconsin, United States
  • Reese, Shannon, University of Wisconsin Madison, Madison, Wisconsin, United States
  • Ptak, Lucille D., University of Wisconsin Madison, Madison, Wisconsin, United States
  • Redfield, Robert R., University of Wisconsin Madison, Madison, Wisconsin, United States
  • Panzer, Sarah E., University of Wisconsin Madison, Madison, Wisconsin, United States
Background

Chronic antibody mediated rejection (cAMR) is a leading cause of kidney graft loss. In many instances, mixed chronic AMR and cellular rejection are observed. We examined B and T cell populations in the lymphoid organs of a sensitized rat kidney transplant model. We hypothesized that sensitized recipients would have increased populations of memory and proinflammatory B and T cells in lymphoid tissues.

Methods

Minor mismatch kidney transplantation was performed to generate cAMR. The cAMR model had 3 groups: 1) syngeneic (Syn, Lewis donor to Lewis recipient), 2) allogeneic (Allo, Fisher donor to Lewis recipient), and 3) sensitized (Sens Allo, Fisher donor to Lewis recipient that received blood transfusion 21 days pre-transplant). Animals were harvested at 6 months post-transplant and lymphoid cells were analyzed by flow cytometry.

Results

Sensitized recipients demonstrated increased numbers of nonswitched and memory B cells in the bone marrow compared to allogeneic recipients (Figure 1). Sensitized recipients demonstrated increased numbers of splenic CD4+ T cells compared to allogeneic recipients. However, splenic CD8+ T cells and T regulatory cell numbers were similar between sensitized and allogeneic recipients. Additionally, splenic T follicular helper (Tfh) cells were elevated in sensitized recipients compared to allogeneic recipients.

Conclusion

We show sensitized kidney transplant recipients with cAMR develop increased populations of memory B cells and CD4+ T cells, including Tfh cells. The interactions of CD4+ T cells, including Tfh cells, with B cells promote the generation of memory B cells and antibody production and support a role for T and B cells in chronic rejection.

Funding

  • Other NIH Support