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.
authors.affiliation: Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Holland
authors.forename: Johannes L
authors.initials: JL
authors.lastname: Zakrzewski
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Tsai
authors.forename: Alan M
authors.initials: AM
authors.lastname: Hanash
authors.forename: Jarrod A
authors.initials: JA
authors.lastname: Dudakov
authors.forename: Odette M
authors.initials: OM
authors.lastname: Smith
authors.forename: Mallory L
authors.initials: ML
authors.lastname: West
authors.forename: Natalie V
authors.initials: NV
authors.lastname: Singer
authors.forename: Jessie
authors.initials: J
authors.lastname: Brill
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Sun
authors.forename: Marcel R M
authors.initials: MR
authors.lastname: van den Brink
mesh_terms: D019264:Adoptive Transfer; D000367:Age Factors; D000818:Animals; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D008198:Lymph Nodes / Q000166:cytology; D008643:Mesentery / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D050778:NFATC Transcription Factors / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D013950:Thymus Gland / Q000166:cytology
chemical_list: D050778:NFATC Transcription Factors; D011948:Receptors, Antigen, T-Cell