First Author | Barata JT | Year | 2006 |
Journal | Exp Hematol | Volume | 34 |
Issue | 9 | Pages | 1133-42 |
PubMed ID | 16939806 | Mgi Jnum | J:116264 |
Mgi Id | MGI:3693403 | Doi | 10.1016/j.exphem.2006.05.001 |
Citation | Barata JT, et al. (2006) Molecular and functional evidence for activity of murine IL-7 on human lymphocytes. Exp Hematol 34(9):1133-42 |
abstractText | Although interleukin-7 (IL-7) is essential for human and murine lymphopoiesis and homeostasis, clear disparities between these species regarding the role of IL-7 during B-cell development suggest that other, subtler differences may exist. One basic unsolved issue of IL-7 biology concerns cross-species activity, because in contrast to the human ortholog, the ability of murine (m)IL-7 to stimulate human cells remains unresolved. Establishing whether two-way cross-species reactivity occurs is fundamental for evaluating the role of IL-7 in chimeric human-mouse models, which are the most versatile tools for studying human lymphoid development and disease in vivo. Here, we show that mIL-7 triggers the same signaling pathways as human (h)IL-7 in human T cells, promoting similar changes in viability, proliferation, size, and immunophenotype, even at low concentrations. This ability is not confined to T cells, because mIL-7 mediates cell growth and protects human B-cell precursors from dexamethasone-induced apoptosis. Importantly, endogenous mIL-7 produced in the mouse thymic microenvironment stimulates human T cells, because their expansion in chimeric fetal thymic organ cultures is inhibited by a mIL-7-specific neutralizing antibody. Our results demonstrate that mIL-7 affects human lymphocytes and indicate that mouse models of human lymphoid development and disease must integrate the biological effects of endogenous IL-7 on human cells. |