Faculty Opinions recommendation of A cluster of coregulated genes determines TGF-beta-induced regulatory T-cell (Treg) dysfunction in NOD mice.

Regulatory T cell (Treg) insufficiency licenses the destruction of insulin-producing pancreatic b cells by auto-reactive effector T cells (Teffs), causing spontaneous autoimmune diabetes in non‑obese diabetic (NOD) mice. We investigated the contribution to diabetes of the TCR repertoires of naive regulatory T cells (nTregs), activated/memory Tregs (amTregs), and CD4<sup>+</sup> Teffs from prediabetic NOD mice and normal C57BL/6 (B6) mice. NOD mice amTreg and Teff repertoire diversity was unexpectedly higher than that of B6 mice. This was due to the presence of highly expanded clonotypes in B6 amTregs and Teffs that were largely lost in their NOD counterparts. IL-2 administration to NOD mice restored such amTreg clonotype expansions and prevented diabetes development. In contrast, IL-2 administration only led to few or no clonotype expansions in nTregs and Teffs, respectively. Noteworthily, IL-2 expanded amTreg and nTreg clonotypes were markedly enriched in islet-antigen specific TCRs. Altogether, our results highlight the link between a reduced clonotype expansion within the activated Treg repertoire and the development of an autoimmune disease. They also indicate that the repertoire of amTregs is amenable to rejuvenation by IL-2.

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Faculty Opinions recommendation of Regulatory T cell (Treg) subsets return in patients with refractory lupus following stem cell transplantation, and TGF-beta-producing CD8+ Treg cells are associated with immunological remission of lupus.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1167979.630084 ◽

2009 ◽

Author(s):

Laurence Morel

Keyword(s):

Stem Cell ◽

T Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Regulatory T Cell ◽

Treg Cells ◽

Tgf Beta

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Impaired Activated/Memory Regulatory T Cell Clonal Expansion Instigates Diabetes in NOD Mice

10.2337/figshare.13611020.v2 ◽

2021 ◽

Author(s):

Vanessa Mhanna ◽

Gwladys Fourcade ◽

Pierre Barennes ◽

Valentin Quiniou ◽

Hang P. Pham ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Regulatory T Cell ◽

Autoimmune Diabetes ◽

Nod Mice ◽

Repertoire Diversity ◽

Pancreatic B Cells ◽

Diabetes Development ◽

Islet Antigen ◽

Cell Clonal Expansion

Regulatory T cell (Treg) insufficiency licenses the destruction of insulin-producing pancreatic b cells by auto-reactive effector T cells (Teffs), causing spontaneous autoimmune diabetes in non‑obese diabetic (NOD) mice. We investigated the contribution to diabetes of the TCR repertoires of naive regulatory T cells (nTregs), activated/memory Tregs (amTregs), and CD4<sup>+</sup> Teffs from prediabetic NOD mice and normal C57BL/6 (B6) mice. NOD mice amTreg and Teff repertoire diversity was unexpectedly higher than that of B6 mice. This was due to the presence of highly expanded clonotypes in B6 amTregs and Teffs that were largely lost in their NOD counterparts. IL-2 administration to NOD mice restored such amTreg clonotype expansions and prevented diabetes development. In contrast, IL-2 administration only led to few or no clonotype expansions in nTregs and Teffs, respectively. Noteworthily, IL-2 expanded amTreg and nTreg clonotypes were markedly enriched in islet-antigen specific TCRs. Altogether, our results highlight the link between a reduced clonotype expansion within the activated Treg repertoire and the development of an autoimmune disease. They also indicate that the repertoire of amTregs is amenable to rejuvenation by IL-2.

Download Full-text