Thymic peptides in immune reconstitution and clinical outcome after allogeneic hematopoietic cell transplantation

Abstract

Patients with hematologic malignancies or nonmalignant diseases may undergo allogeneic hematopoietic cell transplantation (HCT), which represents a potential curative treatment. However, they are still at risk of life-threatening complications, such as relapse, acute graft-versus-host disease, and opportunistic infections. These complications are more likely if T-cell reconstitution is delayed during the initial 3 to 4 months after HCT. Therefore, it is of clinical importance to advance early peripheral T-cell expansion. The thymus is the cradle of T-cell production, but it is extremely sensitive to conditioning drugs used in HCT. As a result, egress of T cells from the thymus is abrogated during the first 3 to 6 months after HCT. Instead, early T-cell reconstitution depends on peripheral expansion of engrafted donor T cells. However, besides its established function to produce T cells, the thymus also produces thymic peptides with hormone-like activity. These molecules play an essential part in the development and nature of immune responses and may have a role in modulating T-cell expansion and function after HCT. In this review, we investigate the role of thymic peptides in shaping the dynamics of immune reconstitution early after HCT. Furthermore, we summarize current reports on clinical application of thymic peptides post-HCT and discuss their potential use in improving patient outcomes.