A Mouse Model of Vascularized Heterotopic Spleen Transplantation for Studying Lymphocyte Biology and Transplant Immunity
1Comprehensive Transplant Center, Department of Surgery, Northwestern University, Chicago, IL, 2Northwestern University, Chicago, IL, 3Department of Surgery, Northwestern University, Chicago, IL
Meeting: 2019 American Transplant Congress
Abstract number: D147
Keywords: B cells, FACS analysis, Mixed chimerism, T cells
Session Information
Session Name: Poster Session D: Lymphocyte Biology: Signaling, Co-Stimulation, Regulation
Session Type: Poster Session
Date: Tuesday, June 4, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: Spleen-derived lymphocytes and myeloid cell populations are critical to the development of organ transplant ischemia-reperfusion injury (IRI) and allograft rejection. In this study, we introduce a modified mouse model of vascularized heterotopic spleen transplantation, which can be utilized to study the function and behavioral activity of splenic-immune cell subsets in transplant IRI and allograft rejection.
*Methods: BALB/c CD45.1 mice were used as spleen donors and BALB/c CD45.2 mice were used as recipients. The main surgical steps included donor spleen harvest, the removal of recipient native spleen, and spleen graft revascularization. Immune cell phenotypes in lymphoid organs including spleen, blood, lymph nodes, and bone marrow, and in non-lymphoid organs including kidney and lung were analyzed by multicolor flow cytometry.
*Results: At the post-operative day (POD) 1, 51 ± 7% (mean ± SD, same as below) of the spleen cells were donor-derived and 46 ± 3% were recipient-derived. At POD7, donor-derived leukocytes accounted for 32 ± 10 % of total spleen cells and recipient-derived cells were up to 56 ± 13%. Donor-derived leukocytes migrated into blood, lymph nodes, and bone marrow as early as POD1 and maintained at day 7, generating a unique chimera valuable for splenocyte trafficking research. Moreover, at day 1 post-transplantation, around 30% of recipient-derived leukocytes were granulocytes (CD11b+Ly6G+), while majority of the myeloid cells retained in the spleen graft were macrophage/dendritic cells (CD11b+F4/80+CD11c+). At POD60, donor-derived lymphocytes and myeloid cells were also detectable in kidney and lung tissue, demonstrating that the spleen was involved in the maintenance of homeostasis of immune cells residing in non-lymphoid organs.
*Conclusions: The mouse model of vascularized spleen transplantation allows the tracking of fate, longevity, and function of splenocytes during steady state and in a disease setting, thereby offering a great opportunity to discover the distinct role for spleen-derived immune cells in transplant immunity or other pathological processes.
To cite this abstract in AMA style:
Qiu L, Wang J, Fernandez R, Yeap X, Han S, Zheng F, Lin C, Zhang ZJ. A Mouse Model of Vascularized Heterotopic Spleen Transplantation for Studying Lymphocyte Biology and Transplant Immunity [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/a-mouse-model-of-vascularized-heterotopic-spleen-transplantation-for-studying-lymphocyte-biology-and-transplant-immunity/. Accessed May 9, 2025.« Back to 2019 American Transplant Congress