Homeostasis of Mature T Cells.

The overall size and composition of the mature T cell pool is regulated by homeostatic mechanisms. A hallmark of homeostatic regulation is the ability of the T cells to undergo spontaneous “homeostatic” proliferation in response to severe lymphopenia. By defining the factors that drive such homeostatic proliferation, we have determined that homeostasis of naïve and memory T cells is controlled by signals from contact with self-MHC/peptide ligands and/or two cytokines, namely IL-7 and IL-15. In addition, we have recently described a simple and highly effective way to administer IL-2, IL-7, IL-15, and other cytokines to strongly expand selective populations of T cell under normal physiological conditions. This new approach overcomes the current limitations that prevent therapeutic use of these essential T cell regulators in their native form. Identification of these homeostatic factors has already proven to be highly clinically relevant in devising novel therapeutic modalities for treatment of cancer and restoration of the immune deficiency from lympho-depleting regiments and advanced aging. The new method of delivering exogenous cytokines should further expand the clinical applicability of homeostatic cytokines.