Houston Methodist researchers, led by Wenhao Chen, PhD, Associate Professor of Transplant Immunology in Surgery, are advancing the field with the identification of a troublesome subset of CD4+ T cells that may be a more effective therapeutic target for preventing transplant rejection in patients.

To gain deeper insight into the role of CD4+ T cells in transplant rejection, Chen’s study utilized single-cell RNA sequencing to analyze the CD4+ T cell response in transplantation scenarios. The results, published in Nature Immunology, indicate the presence of stemlike CD4+ T cells in transplant recipients, as well as the stem-like program directing the CD4+ T cell response in models of transplantation. More specifically, they found stem-like CD4+ T cells which recognize transplant antigens that can differentiate into effector cells that attack transplanted organs. However, the effector cells lose their ability to proliferate and fail to reject allografts upon adoptive transfer into new recipients. These results provide robust evidence for a stem-like program that controls the self-renewal and effector differentiation abilities of CD4+ TEP cells. Because the stem-like CD4+ T cells continually replenish the effector cell pool, they may be the more effective therapeutic target for preventing transplant rejection and in other T cell-related immunotherapies “The identification of these stem-like CD4+ T cells as a key driver of transplant rejection opens a promising new frontier in clinical transplant care. By targeting these cells specifically, we could enhance our ability to prevent rejection, improve long-term outcomes, and ultimately offer patients a better chance at a healthy life with their new organs,” said R. Mark Ghobrial, MD, PhD, J.C. Walter Jr. Presidential Distinguished Chair and Director of the J.C. Walter Jr. Transplant Center. “This work brings us closer to personalized, precision therapies that could one day redefine transplantation success.”