Regulation of an extrathymic T-cell development pathway by oncostatin M

Most of the T lymphocytes that populate the immune system develop in the thymus before its involution during late adolescence. Therefore, subsequent losses in T cells caused by HIV infection, chemotherapy or age-related factors can greatly diminish immune responses to new antigenic challenge. Here we report the discovery of a thymus-independent pathway of T-cell development that may provide help for T-cell immunodeficiency. We show that expression of an oncostatin M transgene in the early T lineage stimulates a dramatic accumulation of immature and mature T cells in lymph nodes. A functional thymus is not required for this effect as reconstitution of nu/nu mice with transgenic bone marrow stimulated a 500-fold increase in Thy-1+ lymph node cells and restored immune responsiveness to allogeneic mouse melanoma cells. This lymphopoietic pathway is not unique to transgenic mice because administration of oncostatin M protein produced a similar response in non-transgenic mice. These results identify a new pathway of T-cell development and a potential treatment for T-cell immunodeficiency with oncostatin M.