Regulation of extrathymic T cell development and turnover by oncostatin M

Chronic exposure to oncostatin M (OM) has been shown to stimulate extrathym ic T cell development. The present work shows that in OM transgenic mice, 1 ) massive extrathymic T cell development takes place exclusively the lymph nodes (LNs) and not in the bone marrow, liver, intestines, or spleen; and 2 ) LNs are the sole site where the size of the mature CD4(+) and CD8(+) T ce ll pool is increased (6- to 7-fold). Moreover, when injected into OM transg enic mice, both transgenic and nontransgenic CD4(+) and CD8(+) T cells pref erentially migrated to the LNs rather than the spleen. Studies of athymic r ecipients of fetal liver grafts showed that lymphopoietic pathway modulated by OM was truly thymus independent, and that nontransgenic progenitors cou ld generate extrathymic CD4(+)CD8(+) cells as well as mature T cells under the paracrine influence of OM, The progeny of the thymic-independent differ entiation pathway regulated by OM was polyclonal in terms of V beta usage, exhibited a phenotype associated with previous TCR ligation, and displayed a rapid turnover rate (5-bromo-2'-deoxyuridine pulse-chase assays). This wo rk suggests that chronic exposure to OM 1) discloses a unique ability of LN s to sustain extrathymic T cell development, and 2) increases the number an d/or function of LN niches able to support seeding of recirculating mature T cells. Regulation of the lymphopoietic pathway discovered in OM transgeni c mice could be of therapeutic interest for individuals with thymic hypopla sia or deficient peripheral T cell niches.