Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 122, Issue 12, Pages 4716-4726Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI60630
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Funding
- NIH [R01-HL069929, R01-CA107096, R01-AI080455, T32 AIO7621, K08CA160659-01]
- US Department of Defense: USAMRAA award [W81XWH-09-1-0294]
- Radiation Effects Research Foundation,(RERF-NIAID)
- Experimental Therapeutics Center of Memorial Sloan-Kettering Cancer Center
- William H. Goodwin and Alice Goodwin
- Lymphoma Foundation
- Alex's Lemonade Stand
- Geoffrey Beene Cancer Research Center at Memorial Sloan-Kettering Cancer Center
- Peter Solomon Fund
- Starr Stem Cell Scholar Fellowship
- CRI Tumor Immunology Predoctoral Fellowship
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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 TCR alpha beta T cells with a broad V beta 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.
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