25 October 2021
New clues to help prevent organ transplant rejection
Published online 22 March 2021
T cells that form in graft tissue contribute to chronic rejection of transplanted kidneys in mice.
Tissue-resident memory T cells (TRM) play key roles in mediating protective immunity at barrier tissues, such as the skin, gut, lung and reproductive tract. But it has been unclear if these specific cells are involved in organ transplantation rejection.
Now, a team of medical scientists in the US and Lebanon presents evidence that TRM from the recipient form in transplanted organs, and that their persistent exposure to the transplant’s antigen signals does not exhaust them. Ultimately, these cells can cause organ rejection.
The team used a mouse model of kidney transplantation and showed that the recipient’s antigen-specific effector T cells, which are involved in steering immune responses, differentiated into TRM, and were very active and proliferated in the graft. They were also able to produce interferon gamma (a cytokine that promotes inflammation) when taken out of the graft and restimulated with donor cells, confirming their memory identity and functionality. The vast majority of graft-residing TRM also lacked the typical features of exhausted cells and their depletion prolonged graft survival.
Finding ways to suppress TRM in the graft could therefore improve transplantation outcomes. “By identifying and deeply characterizing this special subset of T cells down to the gene expression level, we can now — using manual and AI-based approaches — investigate possible gene or protein targets,” says the study’s lead author, Khodor Abou-Daya, of the University of Pittsburgh’s Thomas E. Starzl Transplantation Institute. “Identifying genes or proteins unique to TRM will catalyze the discovery of new or improved therapeutic modalities.”
Abou-Daya, K. I. et al. Resident memory T cells form during persistent antigen exposure leading to allograft rejection. Sci. Immunol. 6, eabc8122 (2021).