Back to Search
Start Over
Cross-Activation of Regulatory T Cells by Self Antigens Limits Self-Reactive and Activated CD8 + T Cell Responses.
- Source :
- International Journal of Molecular Sciences; Sep2023, Vol. 24 Issue 18, p13672, 15p
- Publication Year :
- 2023
-
Abstract
- The interaction between regulatory T (Treg) cells and self-reactive T cells is a crucial mechanism for maintaining immune tolerance. In this study, we investigated the cross-activation of Treg cells by self-antigens and its impact on self-reactive CD8<superscript>+</superscript> T cell responses, with a focus on the P53 signaling pathway. We discovered that major histocompatibility complex (MHC) I-restricted self-peptides not only activated CD8<superscript>+</superscript> T cells but also induced the delayed proliferation of Treg cells. Following HLA-A*0201-restricted Melan-A-specific (pMelan) CD8<superscript>+</superscript> T cells, we observed the direct expansion of Treg cells and concurrent suppression of pMelan<superscript>+</superscript>CD8<superscript>+</superscript> T cell proliferation upon stimulation with Melan-A peptide. Transcriptome analysis revealed no significant alterations in specific signaling pathways in pMelan<superscript>+</superscript>CD8<superscript>+</superscript> T cells that were co-cultured with activated Treg cells. However, there was a noticeable upregulation of genes involved in P53 accumulation, a critical regulator of cell survival and apoptosis. Consistent with such observation, the blockade of P53 induced a continuous proliferation of pMelan<superscript>+</superscript>CD8<superscript>+</superscript> T cells. The concurrent stimulation of Treg cells through self-reactive TCRs by self-antigens provides insights into the immune system's ability to control activated self-reactive CD8<superscript>+</superscript> T cells as part of peripheral tolerance, highlighting the intricate interplay between Treg cells and CD8<superscript>+</superscript> T cells and implicating therapeutic interventions in autoimmune diseases and cancer immunotherapy. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 16616596
- Volume :
- 24
- Issue :
- 18
- Database :
- Complementary Index
- Journal :
- International Journal of Molecular Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 172423921
- Full Text :
- https://doi.org/10.3390/ijms241813672