Transplant Rejection and TNFRSF25

Organ or tissue transplants are a vital process that literally provide new life for its recipients. The first kidney transplant attempt took place in 1935 and failed almost immediately because the blood types were mismatched between the host and donor. In 1954, the first successful kidney transplant occurred between two identical twins.

The greatest transplant story ever told. The Six Million Dollar Man®
There are many types of grafts (see below for more details), but the one most people are familiar with are allografts (graft from a genetically different member of the same species). Allograft rejection occurs when the recipient's immune system senses the newly implanted organ/tissue is foreign and targets it for destruction.
What causes a transplant rejection? There are two main factors involved: Blood group and MHC compatibility. First, both the host and donor must possess ABO-compatible blood groups (ABO antigens are expressed on red blood cells, epithelial and endothelial cells). If this is not correctly matched, the donor cells will be attacked through antibody-mediated lysis.
MHC (major histocompatibility complex) I is expressed by all nucleated cells, and MHC II is expressed primarily by antigen presenting cells (APCs). Both MHC I and II present peptide antigen to T cells. If the molecules are not matched properly, the host T cells will see the donor MHCs as foreign and target the cells for destruction. MHCs and ABO blood groups are properly matched through testing prior to the transplant.

Transplant rejection in a nutshell.
Even if MHCs and blood types are properly matched, additional drug treatments that induce immunosuppression are required to prevent rejection. Recently, an intriguing marker (TNFRSF25: tumor necrosis factor-receptor superfamily 25) has been found on Tregs, which are proficient in suppressing inflammatory responses. When injected, an antibody against TNFRSF25 led to an increase in the Treg populations in mice, preventing the rejection of a cardiac allograft (Wolf, D. et al. 2012. Transplantation. 94:569).

Wood, K.J. & Sakaguchi, S. 2003. Nat. Rev. Immunol. 3:199.
This, of course, presents an interesting development if it can be used to successfully increase rates of allograft transplantation. Should you want to conduct your own experiments with anti-DR3 (TNFRSF25), you can find our reagent here. The data provided below is our own in-house test confirming Treg expansion with the anti-DR3 antibody.
C57BL/6 mice were IP injected with 100 µg LEAF™ purified DR3 (TNFRSF25, clone 4C12) (3 mice) or LEAF™ purified Armenian hamster IgG (3 mice). On day 0, 3, 6, 7 and 11, the blood was drawn and stained with CD4-APC, followed by intracellular staining with Foxp3-PE. The data was analyzed as a percentage of Foxp3-positive cells to total CD4-positive cells. Error bars are +/- SD. ***p < 0.001 between 4C12 and isotype injection.
If you want to learn more about Tregs, check out our page here. Do you have any comments on transplantation? Contact us here.

Just when I thought I got the hang of science…
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