Extrathymic development of murine T cells after bone marrow
transplantation |
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| Authors: | Amanda M. Holland Johannes L. Zakrzewski Jennifer J. Tsai Alan M. Hanash Jarrod A. Dudakov Odette M. Smith Mallory L. West Natalie V. Singer Jessie Brill Joseph C. Sun Marcel R.M. van den Brink |
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| Affiliation: | 1Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. 2Department of Immunology, Weill Cornell Graduate School of Medical Sciences, New York, New York, USA. 3Department of Pediatrics and 4Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. |
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| Abstract: | Restoring T cell competence is a significant clinical challenge in patients whosethymic function is severely compromised due to age or cytoreductive conditioning.Here, we demonstrate in mice that mesenteric LNs (MLNs) support extrathymic T celldevelopment in euthymic and athymic recipients of bone marrow transplantation (BMT).Furthermore, in aged murine BMT recipients, the contribution of the MLNs to thegeneration of T cells was maintained, while the contribution of the thymus wassignificantly impaired. Thymic impairment resulted in a proportional increase inextrathymic-derived T cell progenitors. Extrathymic development in athymic recipientsgenerated conventional naive TCRαβ T cells with a broadVβ repertoire and intact functional and proliferative potential.Moreover, in the absence of a functional thymus, immunity against known pathogenscould be augmented using engineered precursor T cells with viral specificity. Thesefindings demonstrate the potential of extrathymic T cell development for T cellreconstitution in patients with limited thymic function. |
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