T-cell development: an extrathymic perspective

The lymph nodes (LNs) harbor a cryptic T-lymphopoietic pathway that is dramatically amplified by oncostatin M (OM). OM-transgenic mice generate massive amounts of T lymphocytes in the absence of Lin(-)c-Kit(hi)IL-7R alpha(-) lymphoid progenitors and of reticular epithelial cells. Extrathymic T cells that develop along the OM-dependent LN pathway originate from Lin(-)c-Kit(lo)IL-7R alpha(+) lymphoid progenitors and are different from classic T cells in terms of turnover kinetics and function. Positive selection does not obey the same rules in the thymus and the LNs, where positive selection of developing T cells is supported primarily by epithelial and hematopoietic cells, respectively. Extrathymic T cells undergo enhanced homeostatic proliferation and thereby acquire some properties of memory T cells. Following antigen encounter, extrathymic T-cells initiate proliferation and cytokine secretion more readily than classic T cells, but their accumulation is limited by an exquisite susceptibility to apoptosis. Studies on in vitro and in vivo extrathymic T-cell development have yielded novel insights into the essence of a primary T-lymphoid organ. Furthermore, comparison of the thymic and OM-dependent extrathymic pathways shows how the division of labor between primary and secondary lymphoid organs influences the repertoire and homeostasis of T lymphocytes.