Researchers identify immune cells that contribute to transmission rejection

IMAGE: Transplanted kidneys are stained blue showing signs of inflammation. view more

Credit: Martin Oberbarnscheidt

PITTSBURGH, March 19, 2021 – Non-circulating T-memory cells, which play a key role in providing local protection against re-infection, contribute to rejection of malignant transmission, University School of Medicine researchers reveal Pittsburgh in a paper published today in Psychology of science.

The scientists show that the “resident T cells” are harmful in situations where antigens that the cells recognize are present in the body for a long time, such as in organ or transplant cases. -put print. This finding is an important step toward the development of therapies to help prevent organ rejection in transplant recipients.

“Resident memory T cells serve an important diagnostic function,” said co-author Martin Oberbarnscheidt, MD, Ph.D., a professor of surgery at Pitt. “If these cells encounter the same pathogen more than once, they can help with rapid elimination. But studying these cells in transplants gives us a unique opportunity to study what happens when the antigen lasts – a new organ transplant is a large piece of tissue that, unlike disease, stays in the body for a long time. “

Transplant immunologists and surgeons have long recognized that T cells – a subset of immune cells that are at the heart of acquired immune development – play a vital role in the rejection of a transplanted organ. transmitted. But so far, the role of resident memory T cells in rejection of transmission has been neglected.

“Resident T memory cells turn from immune to infection to a problem in a transplant situation while fighting a life-saving organ,” said lead author Khodor Abou-Daya, MD, professor research assistant in the Pitt Department of Surgery. “It’s an elephant in the room – T cells are present at a harmful stage of renal transplant rejection, but no one knew if those cells were active.”

Using a mouse model of renal transplantation, the researchers showed, over time, activated T cells that incorporate a morph organ transplanted into T-resident memory cells.

They found that if they combine blood circulation with two mice, which received both identical renal transplants, T memory cells formed in transplanted organs will not travel from a single mouse. to another man. Similarly, if a transplanted kidney was removed and re-transplanted to another mouse, memory T cells resided in the transplanted kidney and did not spread. anywhere else in the body of the recipient, confirming that these cells reside in the old material permanently.

Surprisingly, despite the presence of the ubiquitous antigen, these resident T memory cells did not become “tired”, as is commonly the case with these T cells during breast infections and tumors. . Instead, the cells remained active, expanding and producing signals that sustained a prolonged immune response. In addition, their formation caused the rejection of a renal graft.

“It is accepted that T cells in transplanted organs or bones are tired and dysfunctional and may not contribute significantly to the rejection of tension,” Abou-Daya said. “Our work shows that T memory cells residing in print are active and destructive.”

Focusing specifically on these cells could improve clinical transmission outcomes while preserving the immune system’s ability to fight disease, reducing side effects. conventional systemic immunosuppressive therapies.

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Other authors of the manuscript include Rayan Rammal, MD, of the American University of Beirut, Lebanon; Roger Tieu, Daqiang Zhao, MD, Faruk Sacirbegovic, Ph.D., Amanda Williams, MS, and Warren Shlomchik, MD, Pitt all. Fadi Lakkis, MD, of Pitt, is a co-author.

This work was supported by the National Institutes of Health (grants AI049466, AI145881, HL143349, AI074490, DK124925, GM008208, 1S10OD011925-01 and 1S10OD019942-01). He was also supported by the Ben J. Lipps Fellowship of the American Nephrology Association and the Thomas E. Starzl Postdoctoral Fellowship in Transplantation Biology.

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About the University of Pittsburgh Schools of Health Sciences

The University of Pittsburgh Schools of Health Sciences include the schools of Medicine, Nursing, Dental Medicine, Pharmacy, Health and Rehabilitation Sciences and the Graduate School of Public Health. The schools serve as an academic partner for the UPMC (University of Pittsburgh Medical Center). Together, the mission is to train healthcare professionals and biochemical scientists of tomorrow, engaging in cutting-edge research that promotes understanding of the causes and cures of disease and participate in the delivery of exceptional patient care. Since 1998, Pitt and its affiliated university faculty have been among the top 10 educational institutions in grant aid from the National Institutes of Health. For more information on the Schools of Health Sciences, visit http: // www.Cheers.pitt.edu.

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