Molecular and functional evidence for activity of murine IL-7 on human lymphocytes.
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.
Barata
Joao T
JT
Institute of Molecular Medicine, Faculty of Medicine of Lisbon University, Lisbon, Portugal. joao_barata@fm.ul.pt
Silva
Ana
A
Abecasis
Miguel
M
Carlesso
Nadia
N
Cumano
Ana
A
Cardoso
Angelo A
AA
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D003907:Dexamethasone / Q000494:pharmacology; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D015851:Interleukin-7 / Q000276:immunology* / Q000494:pharmacology; D038041:Lymphopoiesis / Q000276:immunology*; D051379:Mice; D018448:Models, Immunological; D009924:Organ Culture Techniques; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013045:Species Specificity; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology / Q000276:immunology*
D000893:Anti-Inflammatory Agents; D015851:Interleukin-7; D003907:Dexamethasone