A research study at the University of Chicago has found that, during pregnancy, while a T cell response to a fetus becomes impaired to allow a successful pregnancy, the part of the immune system that makes antibodies (known as the humoral response) become sensitive, forming B memory cells that can contribute to the rejection of a transplanted organ.
The results help clarify why it is possible for the immune system to suffer from fetus during pregnancy, but later on it may be more likely to feel fragile and irritated. refusal of organ transplantation. The study was published on January 4, 2021 in the Journal of Clinical Research.
The defense system is designed to respond and defend against foreign invaders; it does this by recognizing molecules on foreign cells, called antigens, and triggers an immune response that causes T cells to target and attack foreign cells directly, as well as cells memory B which releases antibodies to tag foreign cells for destruction by other blood cells. .
In most cases, this system is extremely beneficial – but when you are pregnant, a little change is needed to prevent fetus rejection, which only shares half of its genes with the fetus. mother and thus secrete foreign antigens to the maternal immune system.
This also has a paradoxical effect on increasing the risk of rejection for a transplanted organ (or allograft) after a person has given birth, especially if the transplanted organ is like a kidney from the father of their children.
This new research was inspired by previous work showing that T cells become tolerized during pregnancy, meaning they do not respond to fetal antigens. “This was paradoxical for the referral field, where we believe pregnancy is a sensitive event,” said co-author Anita Chong, PhD, professor of surgery at UChicago. “I wanted to find out why pregnancy was due to the sensation of an allograft (transplanted organ) from the male partner, but developed a better tolerance for the fetus expressing the same antigens. “
In the study, the researchers examined the immune response of female mice after receiving a transplanted heart from one of their children. By monitoring both T cell response and humoral response, they were able to track both arms of the immune response and study their effect on transmission rejection. They observed that the T cells did not respond to the allograft, but the B-memory cells did, releasing antibodies against foreign antigens from the transplanted heart.
“Our assumption was that both arms of the immune system would be inserted into the transmitting organ that matches children,” Chong said, “But something about the fetus promotes T cell tolerance. which is also reserved for the allograft. On the other hand, the antibodies given to the fetus do not harm the fetus, but cause rejection of the allograft. “
Given the biology of pregnancy, the researchers say, these results make sense.
“Pregnancy cannot progress to completely eradicate the humoral response because it is essential for a mother to be able to produce antibodies against infectious pathogens during pregnancy and by working on the breast This is the only protection a mother can give their baby, so the immune system is primed by making antibodies against anything foreign during this time, including those who expressed the fetus, “Chong said. “As a result, the placenta has developed ways to manipulate these antibodies to prevent fetal rejection in subsequent pregnancies.”
These results are a promising start to preventing transmission relapse in humans after future pregnancies.
“There is potential to implement therapies that destroy B memory cells and antibodies that now make it more difficult for these women to accept a transplant,” said co-author Maria-Luisa Alegre, MD / PhD, professor of medicine at UChicago. “This would benefit women with children. We could rule out antibodies and B cells before transplantation and eliminate the problem, while T cell responses to shared antigens with the fetus and transmission already partially eliminated. “
What is not yet clear is how the fragile humoral response transcends T cell tolerance in allograft rejection in humans after pregnancy, or how T cell tolerance may be induced in non-mothers to prevent rejection in other numbers.
As part of their ongoing collaboration, Chong and Alegre hope to continue working on this puzzle. “One aspect of a future study is to see if we can take advantage of this potential of pregnancy by removing T cells for better absorption not only in pregnant women, but in everyone, “Alegre said. “Outside of pregnancy, humans can develop sensitivity before transmission in a variety of ways, from environmental diseases or antigens, and it can be difficult to protect the transmission from overactive T memory cells. A -now we are looking at how pregnancy can bring these to the point of otherwise difficult T cell memory cells with conventional drugs. “
Source:
University of Chicago Medical Center
Magazine Reference:
Suah, AN, et al. (2021) Fertility-induced humoral sensitization transcends T cell susceptibility to fetal-matching allografts in mice. Journal of Clinical Research. doi.org/10.1172/JCI140715.