In Vivo Instruction of Suppressor Commitment in Naive T Cells

By I. Apostolou, H. von Boehmer. Journal of Experimental Medicine, 2004

822 citations recorded by the source corpus.

The induction of antigen-specific tolerance in the mature immune system of the intact organism has met with limited success. Therefore, nonspecific immunosuppression has been the treatment of choice to prevent unwanted immunity. Here, it is shown that prolonged subcutaneous infusion of low doses of peptide by means of osmotic pumps transforms mature T cells into CD4+25+ suppressor cells that can persist for long periods of time in the absence of antigen and confer specific immunologic tolerance upon challenge with antigen. The described procedure resembles approaches of tolerance induction used decades ago, induces tolerance in the absence of immunity, and holds the promise to become an effective means of inducing antigen-specific tolerance prospectively, whereas its power to suppress already ongoing immune responses remains to be determined.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/4ac527272480e027a369095f5a2ed54319620b6a

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In Immunology

1. Alexander Y. Rudensky
2. Shimon Sakaguchi
3. V. Kuchroo
4. A. O’Garra
5. H. von Boehmer
6. Y. Belkaid
7. J. Bluestone
8. T. Nomura

Citations in the corpus

• Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice (2007, background): “Subsequently, it has been proposed that 'nonregulatory' Foxp3 − T cells specific to self or environmental antigens can also upregulate Foxp3 and acquire regulatory properties in the peripher”
• FOXP3 controls regulatory T cell function through cooperation with NFAT. (2006, neutral): “Thus FOXP3 represses NFAT:AP-1 activity, not by displacing NFAT from NFAT:AP-1 composite sites as suggested previously (Schubert et al., 2001), but rather by forming a cooperative NFAT:FOXP3:DNA complex that re-sembles the cooperative NFAT:Fos:Jun:DNA complex.”
• Mechanisms of suppression by suppressor T cells (2005, background): “Thymic selection seems not to represent the only mode by which CD4 + CD25 + suppressor T cells can be generated because application of agonist peptides in 'subimmunogenic' conditions (low dose and/or lack of costimulation) can convert naive T cells into CD4 + CD25 + suppressor T cell”
• Inducing and expanding regulatory T cell populations by foreign antigen (2005, background): “Intrathymic generation mediated by the process described above does not seem to represent the only mode by which Foxp3 + CD4 + CD25 + T cells can be generated, as suppressor cells with a similar phenotype can be produced de novo from naive CD4 + CD25 − T cells by continuous supply of subimmunoge”
• Regulatory T cells and mechanisms of immune system control (2004, background): “Recently it was shown that CD4 + CD25 − cells from TCR-transgenic mice on a recombination of activating gene (RAG-2)-deficient background, which do not contain thymic-derived regulatory T cells, develop into CD4 + CD25 + regulatory T cells in the periphery and upregulate Foxp3 expression upon enco”
• Potential role of interleukin-10-secreting regulatory T cells in allergy and asthma (2005, background): “These cells originate in the thymus, but cells with similar properties and characteristics can also be induced in the peripher”
• Foxp3+CD25+CD4+ natural regulatory T cells in dominant self‐tolerance and autoimmune disease (2006, background): “This makes them distinct from other adaptive Tregs that differentiate from naı̈ve T cells following antigen exposure in the periphery, although some Tregs that are phenotypically and functionally similar to thymus-produced CD25CD4 natural Tregs may be able to differentiate in the periphery from naı̈”
• Interleukin 4 inhibits TGF-β-induced-Foxp3+T cells and generates, in combination with TGF-β, Foxp3− effector T cells that produce interleukins 9 and 10 (2008, background): “In addition, emerging data suggest that Foxp3 + T cells can also be generated in the peripheral immune compartmen”
• Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation (2007, background): “Antigen exposure without concurrent inflammation may promote conversion of Foxp3 − T cells into Foxp3 + T-re”
• CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells (2006, background): “Moreover, there are several therapeutic interventions that appear to promote T reg cell development and function (10, 11).”