An Alternate Pathway for T Cell Development Supported by the Bone Marrow Microenvironment: Recapitulation of Thymic Maturation

In the principal pathway of α/β T cell maturation, T cell precursors from the bone marrow migrate to the thymus and proceed through several well-characterized developmental stages into mature CD4⁺ and CD8⁺ T cells. This study demonstrates an alternative pathway in which the bone marrow microenvironment also supports the differentiation of T cell precursors into CD4⁺ and CD8⁺ T cells. The marrow pathway recapitulates developmental stages of thymic maturation including a CD4⁺CD8⁺ intermediary cell and positive and negative selection, and is strongly inhibited by the presence of mature T cells. The contribution of the marrow pathway in vivo requires further study in mice with normal and deficient thymic or immune function.