Extrathymic development of murine T cells after bone marrow transplantation Academic Article uri icon

Overview

MeSH Major

  • Bone Marrow Transplantation
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes

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.

publication date

  • December 3, 2012

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3533530

Digital Object Identifier (DOI)

  • 10.1172/JCI60630

PubMed ID

  • 23160195

Additional Document Info

start page

  • 4716

end page

  • 26

volume

  • 122

number

  • 12