Comparative and functional evaluation of in vitro generated to ex vivo CD8 T cells.
The generation of the cytotoxic CD8 T cell response is dependent on the functional outcomes imposed by the intrathymic constraints of differentiation and self-tolerance. Although thymic function can be partly replicated in vitro using OP9-DL1 cell cultures to yield CD8 αβ TCR-bearing cells from hematopoietic progenitor cells, a comprehensive and functional assessment of entirely in vitro generated CD8 T cells derived from bone marrow hematopoietic stem cells has not been established and remains controversial. In this study, we demonstrate that a phenotypic, molecular, and functional signature of in vitro derived CD8 T cells is akin to that of ex vivo CD8 T cells, although several significant differences were also observed. Transfer of in vitro derived CD8 T cells into syngeneic and immunodeficient host mice showed no graft-versus-host response, whereas a robust homeostatic proliferation was observed, respectively. These findings, along with a diverse and broad TCR repertoire expressed by the in vitro derived CD8 T cells, allowed for the successful generation of Ag-specific T cells to be obtained from an entirely in vitro generated CD8 T cell pool. These findings support the use of Ag-specific in vitro derived effector CD8 T cells for immune reconstitution approaches, which would be amenable to further tailoring for their use against viral infections or malignancies.
Duke Scholars
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- Stromal Cells
- Receptors, Antigen, T-Cell
- Mice, Knockout
- Mice, Inbred C57BL
- Mice, Inbred BALB C
- Mice, Congenic
- Mice
- Immunophenotyping
- Immunology
- Hematopoietic Stem Cells
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Stromal Cells
- Receptors, Antigen, T-Cell
- Mice, Knockout
- Mice, Inbred C57BL
- Mice, Inbred BALB C
- Mice, Congenic
- Mice
- Immunophenotyping
- Immunology
- Hematopoietic Stem Cells