How specificity for self-peptides shapes the development and function of regulatory T cells

Abstract

The cataclysmic disease that develops in mice and humans lacking CD4+ T cells expressing the transcription factor Foxp3 has provided abundant evidence that Foxp3+CD4+ Tregs are required to suppress a latent autoreactivity of the immune system. There is also evidence for the existence of tissue-specific Tregs that can act to suppress regional autoimmune responses, suggesting that Tregs exert their effects, in part, through responding to self-peptides. However, how the immune system generates a repertoire of Tregs that is designed to recognize and direct regulatory function to self-peptides is incompletely understood. This review describes studies aimed at determining how T cell recognition of self-peptide(s) directs Treg formation in the thymus, including discussion of a modified "avidity" model of thymocyte development. Studies aimed at determining how TCR specificity contributes to the ability of Tregs to suppress autoimmune diseases are also discussed.

Regulation of autologous immunity to the mouse 5T4 oncofoetal antigen: implications for immunotherapy

“…IFN-c responses may reflect the absence of suitable T cells through depletion of the 5T4-specific helper response during development. Indeed, murine 5T4-specific transcripts were detected in the WT thymus providing for expression of this self-antigen and the capacity for negative deletion of high avidity self-reactive T cells and also the generation of specific natural Treg cells [38]. Hence, the differential ability to drive CD8 ?…”

Human secondary lymphoid organs typically contain polyclonally-activated proliferating regulatory T cells

“…Interestingly, we found that activated Treg populations exhibited a broad TCR-Vb pattern, implying that activation takes place in a polyclonal fashion. As the repertoire of human Tregs is shaped toward recognition of autoantigens, 36 LNs may serve as a place where Tregs interact with their cognate antigen. Support for this notion comes from a mouse study where a portion of naive CD4 pos T cells was found to interact with endogenous antigens in LNs, causing temporary expression of CD69 on these cells.…”

Tregitope: Immunomodulation Powerhouse

“…org/licenses/by-nc-sa/3.0/). development of Tregs expressing defined TCRs [4][5][6]. Among the self-proteins to which tolerance is acutely important for health and homeostasis, immunoglobulins (Ig) are unique.…”