The thymus is a gateway for the production of new T cells, the immune cells responsible for destroying pathogens and precancerous or senescent cells. The thymus is highly active in childhood, churning out a large supply of these immune cells as it builds up and supports the immune system. But upon adulthood the thymus atrophies quickly, reducing that supply to a trickle, and effectively imposing a cap on the number of T cells present in the body at any one time. Unfortunately the evolved mechanisms of the immune system, while very effective in the destruction of most intruders, interact with the presence of persistent herpesviruses - largely cytomegalovirus - to gradually convert useful killer T cells into useless memory T cells fixated on these viruses. Over the years the immune system becomes ever more dysfunctional simply through trying to do its job.
Removing these memory T cells is one possible approach to this issue, to spur the body to generate a replacement set of fresh new cells. Another approach is to increase the supply of new cells, and there are a number of options here ranging from periodic infusions of T cells grown from a patient's own stem cells to restoring the thymus to youthful levels of activity. Here is one example of an attempt to regenerate some of the functions of the thymus:
T cell deficiency related to disease, medical treatment, or aging represents a major clinical challenge and is associated with significant morbidity and mortality in cancer and bone marrow transplantation recipients. This study describes several innovative and clinically relevant strategies to manipulate thymic function based on an interventional radiology technique for intrathymic injection of cells or drugs.
We show that intrathymic injection of multipotent hematopoietic stem/progenitor cells into irradiated syngeneic or allogeneic young or aged recipients resulted in efficient and long-lasting generation of functional donor T cells. Persistence of intrathymic donor cells was associated with intrathymic presence of cells resembling long-term hematopoietic stem cells, suggesting a self-renewal capacity of the intrathymically injected cells. Furthermore, our approach enabled the induction of long-term antigen-specific T cell-mediated anti-tumor immunity following intrathymic injection of progenitor cells harboring a transgenic T cell receptor gene.
The intrathymic injection of interleukin 7 prior to irradiation conferred radioprotection. In addition, thymopoiesis of aged mice improved with a single intrathymic administration of low-dose keratinocyte growth factor, an effect that was sustained even in the setting of radiation-induced injury. Taken together, we established a preclinical framework for the development of novel clinical protocols to establish life-long antigen-specific T cell immunity.