Activation of CD4+ CD25+ regulatory T cell suppressor function by analogs of the selecting peptide.
CD4+ CD25+ Foxp3+ regulatory T (Treg) cells can undergo both thymic selection and peripheral expansion in response to self peptides that are agonists for their T cell receptors (TCR). However, the specificity by which these TCR must recognize peptide:MHC complexes to activate Treg cell function is not known. We show that CD4+ CD25+ Foxp3+ Treg cells can mediate suppression in response to peptides that are only weakly cross-reactive with the self peptide that induced their formation in vivo. Moreover, suppression could be efficiently activated by peptide analogs that were inefficient at inducing CD69 up-regulation, and that also induced little or no proliferation of naïve CD4+ CD25- Foxp3- T cells expressing the same TCR. These findings provide evidence that self peptide-specific CD4+ CD25+ Foxp3+ Treg cells can exert regulatory function in response to self- and/or pathogen-derived peptides with which they are only weakly cross-reactive.
Larkin
Joseph
J
The Wistar Institute, Philadelphia, PA 19104, USA.
Picca
Cristina Cozzo
CC
Caton
Andrew J
AJ
D000818:Animals; D001324:Autoantigens / Q000502:physiology*; D024201:Bystander Effect / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*
D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D000949:Histocompatibility Antigens Class II; C111389:I-Ad antigen; D007166:Immunosuppressive Agents; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell