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Updated: Aug 9, 2026
Mouse Kidney Transplantation: Models of Allograft Rejection
Published on: October 11, 2014
Deficiency of C4 from donor or recipient mouse fails to prevent renal allograft rejection
Tao Lin1, Wuding Zhou, Conrad A Farrar
1Department of Nephrology and Transplantation, 5th Floor, Thomas Guy House, Guy's Hospital, St. Thomas St., London SE1 9RT, UK.
Abstract:
Complement effector products generated in the transplanted kidney are known to mediate transplant rejection, but which of the three main activation pathways of complement trigger this response is unclear. Here we assessed the role of the classical and lectin pathways by studying the common component C4 in mouse kidney transplant rejection. We transplanted wild-type or C4-null H-2(b) donor kidneys into H-2(k) or H-2(d) recipients, or vice-versa, to assess the roles of donor kidney and recipient expression of complement. Intragraft C4 gene expression rose substantially during rejection. However, we found no significant association between graft acceptance and the presence of C4 in either the donor kidney or recipient mouse. At the time of rejection, we found no significant differences in alloantibody response in the different groups. Tubular deposition of C3 to C9 occurred regardless of the absence or presence of C4 in either the donor or recipient mouse, indicating that C4 was dispensable for complement activation at this site. These data suggest that complement activation and renal allograft rejection are independent of the classical and lectin pathways in these models, implying that in the absence of these pathways the alternative pathway is the main trigger for complement-mediated rejection.
Insights
Complement effector products drive transplant rejection, but the specific pathway is unknown. This study found classical and lectin pathways, mediated by C4, are dispensable for kidney transplant rejection in mice.
Area of Science:
- Immunology
- Transplantation Biology
- Renal Medicine
Background:
- Complement system activation is implicated in transplant rejection.
- The specific complement pathways (classical, lectin, alternative) driving renal allograft rejection remain unclear.
Purpose of the Study:
- To investigate the role of the classical and lectin complement pathways in mouse kidney transplant rejection.
- To determine if C4, a component of these pathways, influences graft acceptance or rejection.
Main Methods:
- Utilized C4-null and wild-type mice in kidney transplantation models.
- Assessed intragraft C4 gene expression, alloantibody responses, and complement deposition (C3-C9).
- Evaluated graft acceptance based on donor kidney and recipient C4 expression.
Main Results:
- Intragraft C4 gene expression increased during rejection.
- No significant association was found between graft acceptance and C4 presence in donor or recipient.
- Tubular deposition of C3-C9 occurred irrespective of C4, indicating C4-indispensable complement activation.
- Alloantibody responses did not differ significantly across experimental groups.
Conclusions:
- The classical and lectin complement pathways, mediated by C4, do not appear to be the primary drivers of renal allograft rejection in this mouse model.
- These findings suggest the alternative complement pathway is the main trigger for complement-mediated rejection in the absence of classical and lectin pathway activity.
