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mTOR Inhibition Impairs the Activation and Function of Belatacept-Resistant CD4 + CD57 + T Cells In Vivo and In Vitro.
- Source :
- Pharmaceutics; Apr2023, Vol. 15 Issue 4, p1299, 16p
- Publication Year :
- 2023
-
Abstract
- Calcineurin inhibitors have improved graft survival in solid-organ transplantation but their use is limited by toxicity, requiring a switch to another immunosuppressor in some cases. Belatacept is one option that has been shown to improve graft and patient survival despite being associated with a higher risk of acute cellular rejection. This risk of acute cellular rejection is correlated with the presence of belatacept-resistant T cells. We performed a transcriptomic analysis of in vitro-activated cells to identify pathways affected by belatacept in belatacept-sensitive cells (CD4<superscript>+</superscript>CD57<superscript>−</superscript>) but not in belatacept-resistant CD4<superscript>+</superscript>CD57<superscript>+</superscript> T cells. mTOR was significantly downregulated in belatacept-sensitive but not belatacept-resistant T cells. The inhibition of mTOR strongly decreases the activation and cytotoxicity of CD4<superscript>+</superscript>CD57<superscript>+</superscript> cells. In humans, the use of a combination of mTOR inhibitor and belatacept prevents graft rejection and decreases the expression of activation markers on CD4 and CD8 T cells. mTOR inhibition decreases the functioning of belatacept-resistant CD4<superscript>+</superscript>CD57<superscript>+</superscript> T cells in vitro and in vivo. It could potentially be used in association with belatacept to prevent acute cellular rejection in cases of calcineurin intolerance. [ABSTRACT FROM AUTHOR]
- Subjects :
- GRAFT rejection
T cells
CD4 antigen
GRAFT survival
BELATACEPT
MTOR inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 19994923
- Volume :
- 15
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 163460426
- Full Text :
- https://doi.org/10.3390/pharmaceutics15041299