Reduced positive selection of a human TCR in a swine thymus using a humanized mouse model for xenotolerance induction.
Grace NaumanChiara BorsottiNichole DanzlMohsen Khosravi-MaharlooeiHao-Wei LiEstefania ChavezSamantha StoneMegan SykesPublished in: Xenotransplantation (2019)
Positive selection of T cells expressing the MART1 TCR was inefficient in both a non-selecting human HLA-A2- or swine thymus compared with an HLA-A2+ thymus. Additionally, CD8 MART1 TCRbright T cells were detected in the spleens of mice transplanted with HLA-A2+ thymi but were significantly reduced in the spleens of mice transplanted with swine or HLA-A2- thymi. [Correction added on October 15, 2019, after first online publication: The missing superscript values +, -, and bright have been included in the Results section.] CONCLUSIONS: Positive selection of cells expressing a human-restricted TCR in a transplanted pig thymus is inefficient, suggesting that modifications to improve positive selection of cells expressing human-restricted TCRs in a pig thymus may be necessary to support development of a protective human T-cell pool in future patients.
Keyphrases
- endothelial cells
- mouse model
- pluripotent stem cells
- induced apoptosis
- end stage renal disease
- regulatory t cells
- healthcare
- chronic kidney disease
- newly diagnosed
- peritoneal dialysis
- social media
- cell proliferation
- dendritic cells
- prognostic factors
- oxidative stress
- ejection fraction
- endoplasmic reticulum stress
- patient reported outcomes
- immune response
- high fat diet induced