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A Mouse Model of Vascularized Heterotopic Spleen Transplantation for Studying Spleen Cell Biology and Transplant Immunity
Published on: June 11, 2019
Human immune reconstitution with spleen cells in SCID/Beige mice
B Marcheix1, H Yacoub-Youssef, D Calise
1Inserm U466, CHU Rangueil, Toulouse, France.
Transplantation Proceedings
|September 27, 2005
Summary
Injecting human spleen cells into SCID mice effectively reconstitutes the human immune system, enabling the study of chronic vascular rejection (CVR) in a humanized model.
Area of Science:
- Immunology
- Transplantation Research
- Animal Models
Background:
- Chronic vascular rejection (CVR) is a significant challenge in organ transplantation.
- Existing models using human peripheral blood mononuclear cells (PBMCs) for immune reconstitution in mice often yield incomplete and variable results.
- A more robust method for achieving complete and functional human immune reconstitution is needed to accurately study CVR.
Purpose of the Study:
- To develop and validate an improved method for achieving complete and functional human immune reconstitution in mice.
- To establish a reliable experimental model for studying chronic vascular rejection (CVR) under human allogeneic conditions.
Main Methods:
- Human spleen cells from cadaveric organ donors were injected intraperitoneally into CB.17 SCID/Beige mice.
- Different doses of spleen cells were tested to optimize reconstitution.
- Immune reconstitution was monitored via flow cytometry for circulating human cells (CD3+, CD19+, CD56+) and ELISA for human IgG.
- Lymphoid organ colonization by human cells was assessed using immunohistochemistry and flow cytometry.
- Immune function was evaluated by examining CVR lesions in human arterial grafts.
Main Results:
- Intraperitoneal injection of 30-40 x 10^6 human spleen cells resulted in significant populations of human T (CD3+) and B (CD19+) cells, as well as NK cells (CD56+) in peripheral blood.
- Human T and B cells successfully colonized murine spleen and lymph nodes, with T cells also colonizing the thymus.
- Detectable levels of human IgG were found in mouse serum, and characteristic CVR lesions were observed in the human arterial grafts.
Conclusions:
- Intraperitoneal administration of a specific dose of human spleen cells induces complete and functional human immune reconstitution in CB.17 SCID/Beige mice.
- This optimized method provides a reliable humanized mouse model for investigating chronic vascular rejection (CVR) in a human allogeneic context.
