Coreceptor signal strength regulates positive selection but does not determine CD4/CD8 lineage choice in a physiologic in vivo model.
Journal Article (Journal Article)
TCR signals drive thymocyte development, but it remains controversial what impact, if any, the intensity of those signals have on T cell differentiation in the thymus. In this study, we assess the impact of CD8 coreceptor signal strength on positive selection and CD4/CD8 lineage choice using novel gene knockin mice in which the endogenous CD8alpha gene has been re-engineered to encode the stronger signaling cytoplasmic tail of CD4, with the re-engineered CD8alpha gene referred to as CD8.4. We found that stronger signaling CD8.4 coreceptors specifically improved the efficiency of CD8-dependent positive selection and quantitatively increased the number of MHC class I (MHC-I)-specific thymocytes signaled to differentiate into CD8+ T cells, even for thymocytes expressing a single, transgenic TCR. Importantly, however, stronger signaling CD8.4 coreceptors did not alter the CD8 lineage choice of any MHC-I-specific thymocytes, even MHC-I-specific thymocytes expressing the high-affinity F5 transgenic TCR. This study documents in a physiologic in vivo model that coreceptor signal strength alters TCR-signaling thresholds for positive selection and so is a major determinant of the CD4:CD8 ratio, but it does not influence CD4/CD8 lineage choice.
Full Text
Duke Authors
Cited Authors
- Erman, B; Alag, AS; Dahle, O; van Laethem, F; Sarafova, SD; Guinter, TI; Sharrow, SO; Grinberg, A; Love, PE; Singer, A
Published Date
- November 15, 2006
Published In
Volume / Issue
- 177 / 10
Start / End Page
- 6613 - 6625
PubMed ID
- 17082573
International Standard Serial Number (ISSN)
- 0022-1767
Digital Object Identifier (DOI)
- 10.4049/jimmunol.177.10.6613
Language
- eng
Conference Location
- United States