By B. Kyewski, Elisabeth Suri-Payer
The vertebrate immune approach defends the organism opposed to invading pathogens whereas while being self-tolerant to the body's personal elements hence keeping its integrity. a number of mechanisms act in live performance to make sure self-tolerance. extra tolerance mechanisms, jointly known as dominant tolerance is by way of now firmly verified. it is going to supply new conceptual insights and expectantly new instruments for the sucessful therapy of autoimmune illnesses, stronger melanoma immunotherapy and transplant survival.
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Additional info for CD4+CD25+ Regulatory T Cells: Origin, Function and Therapeutic Potential (Current Topics in Microbiology and Immunology)
Nature 420:502– 507 Bensinger SJ, Bandeira A, Jordan MS, Caton AJ, Laufer TM (2001) Major histocompatibility complex class II-positive cortical epithelium mediates the selection of CD4+ CD25+ immunoregulatory T cells. J Exp Med 194:427–438 Bluestone JA, Abbas AK (2003) Natural versus adaptive regulatory T cells. Nat Rev Immunol 3:253–257 Chen W, Jin W, Hardegen N, Lei, K-J, Li L, Marinos N, McGrady G, Wahl SM (2003) Conversion of peripheral CD4+ CD25– naive T cells to CD4+ CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3.
The ﬁndings of AID resulting from natural mutations (reviewed in Pitkanen and Peterson 2003) or the targeted inactivation (Anderson et al. 2002; Ramsey et al. 2002) of the AIRE transcription factor that regulates promiscuous gene expression on TECs support this conclusion. The observations on the correlation of natural or forced expression of the Foxp3 transcription factor in CD4 T cells with Treg phenotype and function (Fontenot et al. 2003; Hori et al. 2003; Khattri et al. 2003) provided support for the MM96 contention that Treg represent a unique differentiative pathway that is naturally established inside Thymic Commitment of Regulatory T Cells 45 the thymus.
Furthermore, von Boehmer’s group has also reported on the generation of CD25+ TR from peripheral CD25– TCR transgenic x RAGdeﬁcient T cells upon chronic provision of constant levels of the cognate peptide antigen using an osmotic peptide pump as a delivery device (Apostolou and von Boehmer 2004). Thus, these studies serve as a proof of principle that under certain circumstances, such as high levels of TGF-β, CD25+ regulatory T cells can arise from peripheral CD25– T cells upon encounter with their cognate antigen.
CD4+CD25+ Regulatory T Cells: Origin, Function and Therapeutic Potential (Current Topics in Microbiology and Immunology) by B. Kyewski, Elisabeth Suri-Payer