High self-reactivity drives T-bet and potentiates Treg function in tissue-specific autoimmunity

Malt1 Protease Deficiency in Mice Disrupts Immune Homeostasis at Environmental Barriers and Drives Systemic T Cell–Mediated Autoimmunity

“…*p , 0.05, **p , 0.01, ***p , 0.001, ****p , 0.0001. may clonally expand to suppress and oppose the local effector cell activation. Consistently, previous reports suggest that distinct sets of Treg TCRs found in diverse locations confer tissuespecific immunity (60,82,83), and expansion of specific TCR sequences in tissue-draining LNs is characteristic of the activated effector Treg population (84). Despite the in vitro suppressive activity, variable TCR diversity, and effector phenotype in vivo, Malt1PD Tregs were unable to prevent the expansion of pathogenic T cells.…”

ICOS+ Tregs: A Functional Subset of Tregs in Immune Diseases

“…For one thing, it remains confusing how the downstream pathways of ICOS ligation induce Il10 transcription. Recently, the results of many studies have confirmed the correlation between the increased expression of ICOS and the overexpression of CTLA-4, GITR, lag3, TIGIT, and CD69 on Tregs, ( 9 , 15 , 56 , 57 ) and some of these upregulated markers have been shown to be involved in exerting the suppressive function of Tregs through IL-10 induction ( Figure 1 ) ( 58 , 59 ). For example, CD69 + Tregs, which highly express ICOS, were shown to be unable to exert their inhibitory function in Il10 knockout mice ( 57 ).…”

“…CD4 + ICOS + Tregs express high levels of IL-10 but smaller amounts of TGF-β compared with ICOS – Tregs. Transcriptome and FACS analyses have demonstrated a correlation between the increased ICOS expression on Tregs with the high expression levels of CD5, CD69, CXCR3, and T-bet as well as some checkpoint inhibitors, such as CTLA-4, TIGIT, Lag3, and PD-1, ( 15 , 56 , 57 ) some of which have been shown to promote the transcription of the IL-10 gene, contributing to high levels of IL-10 secretion together with ICOS. In addition, other ICOS-expressing regulatory cells, such as Tr1, Treg-of-B cells, and Tfr cells, can also be the source of IL-10.…”

CD4 T Cells Reactive to Hybrid Insulin Peptides Are Indicators of Disease Activity in the NOD Mouse

“…4) Very few 2.5HIPreactive T cells express FoxP3 in the pancreas at the time of disease onset, indicating that restoring immune regulatory function in the 2.5HIP population could be an interesting avenue for immunotherapy. In contrast, insulin-reactive T cells in the pancreas appear to have varying phenotypes and functions, including pathogenic Th1 cells (4,9,34,35), anergic T cells (11), and FoxP3 + T cells (36,37). Our data indicate that insulin tet + cells expressed FoxP3 at a percentage that was higher than that of the bulk CD4 population, particularly in the pancreas, suggesting that this population can also play a regulatory role in disease.…”