Oncostatin M transforms lymphoid tissue function in transgenic mice by stimulating lymph node T-cell development and thymus autoantibody production

Oncostatin M (OM) is a member of the IL-6 subfamily of cytokines that is ex pressed in primary lymphoid tissues such as bone marrow and thymus, as Hell as in secondary lymphoid tissues and activated leukocytes. We produced tra nsgenic mice that overexpressed the human, bo cine, or mouse OM genes and c ompared their relative ability to modulate lymphopoiesis, Each species of c ytokine induced a similar extrathymic pathway of T-cell development involvi ng the accumulation of immature T cells within lymphnodes. Reconstitution e xperiments utilizing lethally irradiated athymic mice indicated that OM had caused hematopoietic precursors within fetal liver and bone marrow to init iate lymphnode T-cell development in the absence of a thymic environment. B reeding experiments with IL6(-/-) and IL-7r alpha(-/-) deficient mice, indi cated that induction of this extrathymic pathway by the OM transgene occurr ed in the absence of IL-6, but was strictly dependent on IL-7 receptor sign aling. Separately, OM stimulated the accumulation of immature B cells withi n the transgenic thymus and caused the subcapsular regions of the thymus to expand with mature B and T cells. This thymus conversion to secondary lymp hoid tissue was responsible for a lethal autoimmune-like disease marked by high titers of circulating autoantibodies, proteinuria, and glomerulonephri tis. The conserved phenotypes elicited by these three forms of OM indicate that this potent hematopoietic cytokine can regulate lymphoid tissue functi on and morphogenesis, (C) 1999 International Society for Experimental Hemat ology, Published by Elsevier Science Inc.