A specific signalling signature characterizes the development of naturally occurring and antigen-specific regulatory T cells.
The molecular signals involved in the generation of thymic regulatory T cells (Treg) still remain controversial. It has been proposed that high avidity interactions are required for Treg selection. Here, we used double transgenic mice (TCR-HA x IgHA) and followed the kinetics and phosphorylation status of HA-specific Tregs that develop in the absence or presence of their agonist ligand expressed in the thymus, as well as of polyclonal "naturally occurring" Tregs (nTregs). We found that, in basal conditions, nTregs showed enhanced basal phosphorylation of c-Cbl, Erk and PI3K, indicating their selection by high avidity ligands. However, in response to TCR cross-linking, both nTregs from Balb/c mice and HA-specific Tregs showed reduced levels of phosphorylated Erk1/2, c-Cbl and Akt. We conclude that thymus-derived Tregs display a characteristic "signalling signature" that suggests qualitative differences in TCR-mediated signalling that may not be explained merely by a higher TCR avidity.
Nava
Karen
K
Departamento de Inmunología. Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Distrito Federal, México.
Ordoñez-Rueda
Diana
D
Sarukhán
Adelaida
A
Chávez-Rios
Jesús R
JR
García-Zepeda
Eduardo A
EA
Soldevila
Gloria
G
D000818:Animals; D002454:Cell Differentiation; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D048052:Mitogen-Activated Protein Kinase 3 / Q000276:immunology / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology / Q000378:metabolism; D050721:Proto-Oncogene Proteins c-cbl / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; C483468:hemagglutinin, human influenza A virus; D050721:Proto-Oncogene Proteins c-cbl; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D048052:Mitogen-Activated Protein Kinase 3