Immune Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation: Time To T Up the Thymus

Abstract

The success of allogeneic hematopoietic stem cell transplantation, a key treatment for many disorders, is intertwined with T cell immune reconstitution. The thymus plays a key role post allogeneic hematopoietic stem cell transplantation in the generation of a broad but self-tolerant T cell repertoire, but it is exquisitely sensitive to a range of insults during the transplant period, including conditioning regimens, corticosteroids, infections, and graft-versus-host disease. Although endogenous thymic repair is possible it is often suboptimal, and there is a need to develop exogenous strategies to help regenerate the thymus. Therapies currently in clinical trials in the transplant setting include keratinocyte growth factor, cytokines (IL-7 and IL-22), and hormonal modulation including sex steroid inhibition and growth hormone administration. Such regenerative strategies may ultimately enable the thymus to play as prominent a role after transplant as it once did in early childhood, allowing a more complete restoration of the T cell compartment.