Number of T reg cells that differentiate does not increase upon encounter of agonist ligand on thymic epithelial cells.
It has been reported that the differentiation of CD4+CD25+ regulatory T cells (T reg cells) can be induced by agonist peptide/major histocompatibility complex ligands in the thymus. Exploiting a transgenic mouse line wherein expression of a particular T cell epitope can be controlled temporally and quantitatively, we found that diversion of differentiating thymocytes into the FoxP3 T reg cell pathway by this agonist ligand was essentially nonexistent. However, CD4+CD25+ thymocytes were much less sensitive than their CD4+CD25- companions, by two to three orders of magnitude, to agonist-induced clonal deletion, such that their proportion increased, giving the false impression of induced differentiation. To account for these and prior observations, one can propose that differentiation along the CD4+CD25+ pathway is induced by cues other than recognition of self-agonist cues, which are poorly read by thymocytes, whose T cell receptors are conducive to selection toward the conventional CD4+CD25- lineage. Thus, selective survival, rather than induced differentiation, may explain the apparent enrichment observed here and in previous studies.
van Santen
Hisse-Martien
HM
Section of Immunology and Immunogenetics, Joslin Diabetes Center, Boston, MA 02215, USA.
Benoist
Christophe
C
Mathis
Diane
D
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D017637:Clonal Deletion / Q000276:immunology*; D018076:DNA, Complementary / Q000235:genetics; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005434:Flow Cytometry; D005802:Genes, MHC Class II / Q000276:immunology; D008024:Ligands; D051379:Mice; D008822:Mice, Transgenic; D015345:Oligonucleotide Probes; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology*
D001324:Autoantigens; D018076:DNA, Complementary; D018984:Epitopes, T-Lymphocyte; D008024:Ligands; D015345:Oligonucleotide Probes; D010455:Peptides