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Effects of IL-7 on Early Human Thymocyte Progenitor Cells In Vitro and in SCID-hu Thy/Liv Mice¹

Laura A. Napolitano^2,*,, Cheryl A. Stoddart^*, Mary Beth Hanley^*, Eric Wieder³ and Joseph M. McCune^*,,

^* Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94141; and Departments of Medicine and Microbiology and Immunology, University of California, San Francisco, CA 94143

IL-7 is a critical component of thymopoiesis in animals and has recently been shown to play an important role in T cell homeostasis. Although there is increasing interest in the use of IL-7 for the treatment of lymphopenia caused by the HIV type 1, evidence that IL-7 may accelerate HIV replication has raised concerns regarding its use in this setting. We sought to identify the effects of IL-7 on human thymocyte survival and to determine the impact of IL-7 administration on in vivo HIV infection of the human thymus. Using in vitro analysis, we show that IL-7 provides potent anti-apoptotic and proliferative signals to early thymocyte progenitors. Analysis of CD34⁺ subpopulations demonstrates that surface IL-7 receptor is expressed on most CD34^highCD5⁺CD1a^- thymocytes and that this subpopulation appears to be one of the earliest maturation stages responsive to the effects of IL-7. Thus, IL-7 provides survival signals to human thymocytes before surface expression of CD1a. CD4⁺CD8⁺ thymocytes are relatively unresponsive to IL-7, although IL-7 protects these cells from dexamethasone-induced apoptosis. IL-7 has a predominantly proliferative effect on mature CD4⁺CD3⁺CD8^- and CD8⁺CD3⁺CD4^- thymocytes. In contrast to the in vitro findings, we observe that in vivo administration of IL-7 to SCID-hu Thy/Liv mice does not appear to enhance thymocyte survival nor does it appear to accelerate HIV infection. Given the growing interest in the use of IL-7 for the treatment of human immunodeficiency, these findings support additional investigation into its in vivo effects on thymopoiesis and HIV infection.

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