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- Title
Extrathymic development of murine T cells after bone marrow transplantation.
- Authors
Holland, Amanda M.; Zakrzewski, Johannes L.; Tsai, Jennifer J.; Hanash, Alan M.; Dudakov, Jarrod A.; Smith, Odette M.; West, Mallory L.; Singer, Natalie V.; Brill, Jessie; Sun, Joseph C.; van den Brink, Marcel R.M.
- Abstract
Restoring T cell competence is a significant clinical challenge in patients whose thymic function is severely compromised due to age or cytoreductive conditioning. Here, we demonstrate in mice that mesenteric LNs (MLNs) support extrathymic T cell development in euthymic and athymic recipients of bone marrow transplantation (BMT). Furthermore, in aged murine BMT recipients, the contribution of the MLNs to the generation of T cells was maintained, while the contribution of the thymus was significantly impaired. Thymic impairment resulted in a proportional increase in extrathymic-derived T cell progenitors. Extrathymic development in athymic recipients generated conventional naive TCRaß T cells with a broad Vß repertoire and intact functional and proliferative potential. Moreover, in the absence of a functional thymus, immunity against known pathogens could be augmented using engineered precursor T cells with viral specificity. These findings demonstrate the potential of extrathymic T cell development for T cell reconstitution in patients with limited thymic function.
- Subjects
T cells; BONE marrow transplantation; CELL growth; THYMUS; PROGENITOR cells; LABORATORY mice
- Publication
Journal of Clinical Investigation, 2012, Vol 122, Issue 12, p1
- ISSN
0021-9738
- Publication type
Article
- DOI
10.1172/JCI60630