Antigen-induced IL-10+ regulatory T cells are independent of CD25+ regulatory cells for their growth, differentiation, and function.
Recent studies have emphasized the importance of T cells with regulatory/suppressor properties in controlling autoimmune diseases. A number of different types of regulatory T cells have been described with the best characterized being the CD25(+) population. In addition, it has been shown that regulatory T cells can be induced by specific Ag administration. In this study, we investigate the relationship between peptide-induced, CD4(+) regulatory T cells and naturally occurring CD4(+)CD25(+) cells derived from the Tg4 TCR-transgenic mouse. Peptide-induced cells were FoxP3(-) and responded to Ag by secreting IL-10, whereas CD25(+) cells failed to secrete this cytokine. Both cell types were able to suppress the proliferation of naive lymphocytes in vitro although with distinct activation sensitivities. Depletion of CD25(+) cells did not affect the suppressive properties of peptide-induced regulators. Furthermore, peptide-induced regulatory/suppressor T cells could be generated in RAG(-/-), TCR-transgenic mice that do not spontaneously generate CD25(+) regulatory cells. These results demonstrate that these natural and induced regulatory cells fall into distinct subsets.
Nicolson
Kirsty S
KS
Department of Cellular and Molecular Medicine, University of Bristol Medical School, University Walk, Bristol, United Kingdom.
O'Neill
Emma J
EJ
Sundstedt
Anette
A
Streeter
Heather B
HB
Minaee
Sophie
S
Wraith
David C
DC
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000235:genetics; D005786:Gene Expression Regulation; D007108:Immune Tolerance / Q000276:immunology; D016753:Interleukin-10 / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D015375:Receptors, Interleukin-2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015375:Receptors, Interleukin-2; D016753:Interleukin-10