Cutting edge: self-peptides drive the peripheral expansion of CD4+CD25+ regulatory T cells.
CD4(+)CD25(+) regulatory T cell selection is initiated by high-specificity interactions with self-peptides in the thymus, although how these cells respond to cytokine-derived signals and to re-exposure to self-peptide:MHC complexes in the periphery is not well understood. We have used a transgenic mouse system, in which the peptide that induces thymic selection of a clonal population of CD4(+)CD25(+) regulatory T cells is known, to show that CD4(+)CD25(+) T cells proliferate in response to their selecting self-peptide in vivo. Moreover, they do not proliferate in response to lymphopenia in the absence of the selecting self-peptide, reflecting a low level of expression of the high affinity receptor for IL-7 (CD127) relative to conventional CD4(+) T cells. That their selecting self-peptide is both required for and promotes the peripheral expansion of CD4(+)CD25(+) regulatory T cells may direct their accumulation in sites where the self-peptide is expressed.
Cozzo
Cristina
C
The Wistar Institute, Philadelphia, PA 19104, USA.
Larkin
Joseph
J
Caton
Andrew J
AJ
D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology / Q000494:pharmacology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation
D001324:Autoantigens; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D020395:Receptors, Interleukin-7