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.
Clegg
C H
CH
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121, USA. christopher_h._clegg@ccmail.bms.com
Rulffes
J T
JT
Wallace
P M
PM
Haugen
H S
HS
D000818:Animals; D016026:Bone Marrow Transplantation; D006133:Growth Substances / Q000235:genetics / Q000502:physiology*; D006411:Hematopoiesis, Extramedullary / Q000502:physiology*; D007121:Immunocompetence; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D053683:Oncostatin M; D010455:Peptides / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology*; D013934:Thymectomy
D006133:Growth Substances; C508352:Osm protein, mouse; D010455:Peptides; D011993:Recombinant Fusion Proteins; D053683:Oncostatin M