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 protecting 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 validated. it is going to provide new conceptual insights and with a bit of luck new instruments for the sucessful therapy of autoimmune illnesses, more desirable melanoma immunotherapy and transplant survival.
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Additional resources for CD4+CD25+ Regulatory T Cells: Origin, Function and Therapeutic Potential (Current Topics in Microbiology and Immunology)
Thus, this in vitro ﬁnding does not exclude the possibility that naturally arising TR function based on recognition of such self-antigen:MHC class II ligands in vivo. Other in vitro evidence in support of CD25+ T cell self-reactivity obtained by limiting dilution cloning in the presence of syngeneic antigen-presenting cells is hard to interpret because of the difﬁculty of assessing the cloning efﬁciency of TR and the possible contamination of TR population with activated T cells with up-regulated CD25 expression (Romagnoli et al.
Proliferation within the naturally arising polyclonal TR populations has also been described in vivo in CSFE dilution or BrDU-labeling experiments (Fisson et al. 2003; Tang et al. 2003). Extrapolating the data described above from TCR transgenic models to these data might suggest then, that naturally arising regulatory T cells are proliferating because of their TCR self-reactivity. However, it is not clear from these data what the precursor frequency of the proliferating cells is. Moreover, the differing proliferative capacity of the CD25+ and CD25– T cell subsets may be explained by distinct properties unrelated to TCR speciﬁcity, such as expression of chemokine receptors or cytokine receptors such as IL-2R.
6 A Large Proportion of Peripheral CD25+ TCRs Have Greater Self-Reactivity than CD25– TCRs The aforementioned paradigm of regulatory T cell development implies that the CD25+ and CD25– TCR repertoires are different, as they are selected based on a different avidity for self-antigen. Our sequencing analyses of the TCR repertoire represented by a variable TRAV14 associated with a transgenic TCRβ chain is consistent with this prediction, as we ﬁnd that there is an overlap estimated at less than 25% between the TCRs isolated between both subsets (Hsieh et al.