Figure 3. Selected strategies to rejuvenate the involuted thymus.

The potential of several hormones and growth factors to rejuvenate the involuted thymus has been tested in various preclinical and clinical trials. Many of these factors can be grouped into three categories. Those in the first (i), such as IL-7, bind to progenitors in the bone marrow and thymus and have only modest effects on thymopoiesis. There is little evidence that IL-7 has effects on thymic stromal cells. Instead, the benefit of IL-7 may lie in its ability to stimulate peripheral T cell survival/expansion. The second category (ii) includes hormones such as GH that have been demonstrated in preclinical and clinical trials to stimulate thymopoiesis and increase thymic size. Many GH effects are mediated through induction of IGF-1. IGF-1 can bind to receptors on thymic stroma and thymocytes, although its actions are primarily mediated through effects on the former cells. Stromal cell–derived factors presumably then act on thymocytes (curved arrow). A third category of factors (iii), typified by FGF7, bind to stromal cells but not thymocytes. Stromal cell–induced factors then act on thymocytes (curved arrow), and we have recently demonstrated that effects include downregulation of Ink4a in ETPs (82). The thymopoietic effects of several additional factors have been evaluated, and recent detailed reviews should be consulted for more information (99, 100).