T‐cell development: an extrathymic perspective

Summary:  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‐7Rα – 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‐7Rα + 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.