New vaccine promotes immune regulation that treats autoimmunity and prolongs transplant survival

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A subtype of CD8 T cells, classically known to promote immune system responses, can actually regulate the immune system by suppressing immune cells that cause self-destructive responses leading to autoimmune disorders and organ graft rejection.

A team led by researchers from the Department of Medicine and Transplant Research Center at Brigham & Women’s Hospital, a founding member of the Mass General Brigham Health Care System, developed a vaccine in preclinical models in collaboration with researchers at the Dana-Farber Cancer Institute. To promote immune regulation. This vaccine uses synthetically modified natural peptides to stimulate CD8 T regulatory cells. Using a mouse model, the researchers discovered that those self-peptides, presented by a certain class of major histocompatibility complex, identify harmful immune cells to attack and eliminate the body’s own regulatory CD8 Tregs.

The vaccine stimulates and propagates those regulatory T cells which in turn keep the harmful cells in check. These cells are crucial for maintaining the immune response and preventing inflammation. The researchers found that the improved vaccine prolonged allograft survival in mice and tested anti-allograft immunity in mismatched kidney transplants. A similar pathway was also identified in humans, suggesting that this research may protect patients with autoimmune disorders or organ transplants.

This new vaccine promotes immune regulation that treats autoimmunity and prolongs kidney allograft survival in mice. “Our research identifies an analogous pathway in humans that we hope to target soon.”

Jamil R. Aji, MD, PhD, co-corresponding author, Brigham’s Transplant Research Center

“The identification of equivalent human T cell receptors in tested mouse models may form the basis of a novel and effective treatment for disorders that reflect an overactive or dysregulated immune system.” This work was done in collaboration with co-corresponding author, Harvey Cantor MD of the Dana-Farber Cancer Institute.


Journal Reference:

Kim, H.J., etc (2023) A narrow T cell receptor repertoire dictates thymic differentiation of MHC class Ib-restricted CD8+ regulatory T-cells.. Journal of Clinical Investigation.

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