Related Experiment Video
Updated: Jul 13, 2026

Generation of Induced Regulatory T Cells from Primary Human Naïve and Memory T Cells
Published on: April 16, 2012
Prevalence of newly generated naive regulatory T cells (Treg) is critical for Treg suppressive function and
Jürgen Haas1, Benedikt Fritzsching, Petra Trübswetter
1Division of Molecular Neuroimmunology, Department of Neurology, University of Heidelberg, Heidelberg, Germany.
Abstract:
The suppressive function of regulatory T cells (T(reg)) is impaired in multiple sclerosis (MS) patients. The mechanism underlying the T(reg) functional defect is unknown. T(reg) mature in the thymus and the majority of cells circulating in the periphery rapidly adopt a memory phenotype. Because our own previous findings suggest that the thymic output of T cells is impaired in MS, we hypothesized that an altered T(reg) generation may contribute to the suppressive deficiency. We therefore determined the role of T(reg) that enter the circulation as recent thymic emigrants (RTE) and, unlike their CD45RO(+) memory counterparts, express CD31 as typical surface marker. We show that the numbers of CD31(+)-coexpressing CD4(+)CD25(+)CD45RA(+)CD45RO(-)FOXP3(+) T(reg) (RTE-T(reg)) within peripheral blood decline with age and are significantly reduced in MS patients. The reduced de novo generation of RTE-T(reg) is compensated by higher proportions of memory T(reg), resulting in a stable cell count of the total T(reg) population. Depletion of CD31(+) cells from T(reg) diminishes the suppressive capacity of donor but not patient T(reg) and neutralizes the difference in inhibitory potencies between the two groups. Overall, there was a clear correlation between T(reg)-mediated suppression and the prevalence of RTE-T(reg), indicating that CD31-expressing naive T(reg) contribute to the functional properties of the entire T(reg) population. Furthermore, patient-derived T(reg), but not healthy T(reg), exhibit a contracted TCR Vbeta repertoire. These observations suggest that a shift in the homeostatic composition of T(reg) subsets related to a reduced thymic-dependent de novo generation of RTE-T(reg) with a compensatory expansion of memory T(reg) may contribute to the T(reg) defect associated with MS.
Related Concept Videos
T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...
Multiple Sclerosis l: Introduction

