Recently a study, published in the journal Immunity, have found a way to prevent transplanted organ rejection, without affecting the ability of the immune system to fight microbial infection. The research was conducted at the University of Basel.
Transplant rejection is a procedure in which a transplant receiver’s immune system attacks the transplanted tissue or organ.
Despite the multiple defense mechanisms which tumor possess to protect themselves against immune-mediated clearance, evidence suggests that modulating the immune environment can help by shifting from immune inactivity to favor anti-tumor reactivity. These findings could pave the way for new methods of reducing transplant rejection in the future.
Organ transplant rejection and infection
Organ transplant rejection occurs when immune cells of the body called T cells to respond to donor organs as if they were foreign attackers like viruses, bacteria, and fungi. Long term transplant survival can be maintained by manipulating or boosting the immune system to decrease the risk of transplant rejection.
Now researchers of the study, Jean Pieters and colleagues, have discovered a way to selectively suppress this reaction to donor organs. They did this by successfully modulating a protein controller of T cells named coronin 1.
The attack to transplanted organs can be prevented by blocking this protein in T cells, without disturbing their ability to repel viruses, bacteria, and fungi. These discoveries could possibly provide new methods for reducing graft rejection in the future.
In a mouse model, the research team observed that eliminating coronin 1 caused T cells vastly to suppress the immune response to a transplanted organ. Also, it actively prevented the transplant rejection. Astonishingly, coronin 1-depleted T cells continue to fight infections at the same time in the body.
Tolerance pathway for organ transplantation
According to the researchers, coronin 1 was initially defined as a host factor which pathogens capture to help them live inside immune cells.
The recent study demonstrates that within T cells, coronin 1 acts as a signaling pathway regulator. It generates a ‘second messenger’ molecule called as cAMP.
After the removal of coronin, the level of cAMP dramatically rises in T cells. This makes them tolerogenic to the transplanted organ. However, Pieters and team found that T cells could still be stirred to control infection as microorganisms promote the expression of molecules which reduce cAMP-mediated suppression.
The study illustrates that the immune system of the body can be manipulated to selectively suppress a host’s reaction to transplanted organs.
Now, researchers face the challenge of translating these discoveries into the development of therapies that will enable tolerance of transplanted organs, whilst retaining the body’s ability to fight infection.