Related Experiment Video
Updated: Jul 30, 2026

Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets
Published on: April 16, 2015
Coreceptor reversal in the thymus: signaled CD4+8+ thymocytes initially terminate CD8 transcription even when
E Brugnera1, A Bhandoola, R Cibotti
1Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA.
Abstract:
A central paradigm of T cell development is that CD4+8+ (DP) thymocytes differentiate into CD4+ or CD8+ T cells in response to intrathymic signals that extinguish transcription of the inappropriate coreceptor molecule. Contrary to this prevailing paradigm, we now demonstrate that signaled DP thymocytes initially terminate CD8 transcription even when differentiating into CD8+ T cells. Remarkably, thymocytes that have selectively terminated CD8 transcription can be signaled by IL-7 to differentiate into CD8+ T cells by silencing CD4 transcription and reinitiating CD8 transcription, events we refer to as "coreceptor reversal." These observations significantly alter our understanding of CD8+ T cell differentiation and lead to a new perspective ("kinetic signaling") on CD4/CD8 lineage determination in the thymus. These observations also suggest a novel mechanism by which bipotential cells throughout development can determine their appropriate cell fate.
Related Concept Videos
Forced Transdifferentiation
Artificial transdifferentiation occurs...
T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...
T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...

