Extrathymic development of murine T cells after bone marrow transplantation Journal Article
| Authors: | Holland, A. M.; Zakrzewski, J. L.; Tsai, J. J.; Hanash, A. M.; Dudakov, J. A.; Smith, O. M.; West, M. L.; Singer, N. V.; Brill, J.; Sun, J. C.; van den Brink, M. R. M. |
| Article Title: | Extrathymic development of murine T cells after bone marrow transplantation |
| 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 TCRαβ T cells with a broad Vβ 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. |
| Keywords: | signal transduction; controlled study; nonhuman; lymph nodes; t lymphocyte; cd8-positive t-lymphocytes; mouse; animals; mice; animal tissue; cells, cultured; cell function; cell maturation; animal experiment; age factors; mice, inbred balb c; mice, inbred c57bl; mice, nude; pre t lymphocyte; thymus; receptors, antigen, t-cell; thymus gland; cd4-positive t-lymphocytes; adoptive transfer; immunity; bone marrow transplantation; ex vivo study; mesentery; coculture techniques; recipient; nfatc transcription factors; mesentery lymph node |
| Journal Title: | Journal of Clinical Investigation |
| Volume: | 122 |
| Issue: | 12 |
| ISSN: | 0021-9738 |
| Publisher: | American Society for Clinical Investigation |
| Date Published: | 2012-12-03 |
| Start Page: | 4716 |
| End Page: | 4726 |
| Language: | English |
| DOI: | 10.1172/jci60630 |
| PROVIDER: | scopus |
| PMCID: | PMC3533530 |
| PUBMED: | 23160195 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 2 January 2013" - "CODEN: JCINA" - "Source: Scopus" |
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MSK Authors
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616Van Den Brink -
119Hanash -
58Dudakov -
52Tsai -
131Sun -
98Smith -
57Zakrzewski -
55Holland -
24Singer -
24West
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