Adaptive TGF-β-dependent regulatory T cells control autoimmune diabetes and are a privileged target of anti-CD3 antibody treatment

You, Sylvaine; Leforban, Bertrand; Garcia, Cyrielle; Bach, Jean‐François; Bluestone, Jeffrey A.; Chatenoud, Lucienne

doi:10.1073/pnas.0701171104

Cited by 163 publications

(142 citation statements)

References 52 publications

Supporting

Mentioning

135

Contrasting

Unclassified

Order By: Relevance

“…In our experiment, the majority of Foxp3 + cells are found in the CD4 + CD25 hi T cells although CD4 + CD25 lo cells also express some level of Foxp3 (Fig. S7 E and F) (32).…”

Section: Il-7rα Antibody Treatment Increases the Frequency But Not Thementioning

confidence: 81%

Anti–IL-7 receptor-α reverses established type 1 diabetes in nonobese diabetic mice by modulating effector T-cell function

Lee

Logronio

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

118

112

View full text Add to dashboard Cite

Genetic variation in the IL-7 receptor-α ( IL-7R ) gene is associated with susceptibility to human type 1 diabetes (T1D). Here we investigate the therapeutic efficacy and mechanism of IL-7Rα antibody in a mouse model of T1D. IL-7Rα antibody induces durable, complete remission in newly onset diabetic mice after only two to three injections. IL-7 increases, whereas IL-7Rα antibody therapy reduces, the IFN-γ–producing CD4 + (T H 1) and IFN-γ–producing CD8 + T cells. Conversely, IL-7 decreases and IL-7Rα antibody enhances the inhibitory receptor Programmed Death 1 (PD-1) expression in the effector T cells. Programmed Death 1 blockade reversed the immune tolerance mediated by the IL-7Rα antibody therapy. Furthermore, IL-7Rα antibody therapy increases the frequency of regulatory T cells without affecting their suppressor activity. The durable efficacy and the multipronged tolerogenic mechanisms of IL-7Rα antibody therapy suggest a unique disease-modifying approach to T1D.

show abstract

“…In our experiment, the majority of Foxp3 + cells are found in the CD4 + CD25 hi T cells although CD4 + CD25 lo cells also express some level of Foxp3 (Fig. S7 E and F) (32).…”

Section: Il-7rα Antibody Treatment Increases the Frequency But Not Thementioning

confidence: 81%

Anti–IL-7 receptor-α reverses established type 1 diabetes in nonobese diabetic mice by modulating effector T-cell function

Lee

Logronio

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

118

112

View full text Add to dashboard Cite

show abstract

“…Furthermore, Treg cell deficiency seems important in the pathogenesis of T1D. [21][22][23][24] Consequently, altered immune regulation in T1D might very well be caused by intestinal dysbiosis, which is most intriguing as stimulation of the mucosal immune system by the gut microbiota may influence the way the immune system discriminates between selfand non-self antigens.…”

Section: Introductionmentioning

confidence: 99%

Gut microbial markers are associated with diabetes onset, regulatory imbalance, and IFN-γ level in NOD Mice

Krych¹,

et al. 2015

View full text Add to dashboard Cite

Gut microbiota regulated imbalances in the host's immune profile seem to be an important factor in the etiology of type 1 diabetes (T1D), and identifying bacterial markers for T1D may therefore be useful in diagnosis and prevention of T1D. The aim of the present study was to investigate the link between the early gut microbiota and immune parameters of non-obese diabetic (NOD) mice in order to select alleged bacterial markers of T1D. Gut microbial composition in feces was analyzed with 454/FLX Titanium (Roche) pyro-sequencing and correlated with diabetes onset age and immune cell populations measured in diabetic and non-diabetic mice at 30 weeks of age. The early gut microbiota composition was found to be different between NOD mice that later in life were classified as diabetic or non-diabetic. Those differences were further associated with changes in FoxP3 C regulatory T cells, CD11b C dendritic cells, and IFN-g production. The model proposed in this work suggests that operational taxonomic units classified to S24-7, Prevotella, and an unknown Bacteriodales (all Bacteroidetes) act in favor of diabetes protection whereas members of Lachnospiraceae, Ruminococcus, and Oscillospira (all Firmicutes) promote pathogenesis.

show abstract

“…Treg in the periphery (Belghith et al 2003). This process is supported by transforming growth factor (TGF)-b1, which is secreted by antigen-presenting cells (APC) in response to anti-CD3 Ab-induced apoptotic Teff (Perruche et al 2008;You et al 2007). In addition, natural Foxp3…”

Section: Anti-cd3 Ab Therapymentioning

confidence: 99%

Reestablishing T Cell Tolerance by Antibody-Based Therapy in Type 1 Diabetes

Morillon

Martin

Gojanovich

et al. 2015

Arch. Immunol. Ther. Exp.

View full text Add to dashboard Cite

Type 1 diabetes (T1D) is an autoimmune disease in which the insulin-producing b cells are selectively destroyed. b cell-specific T cells are considered to be the major mediators of pathology. Accordingly, most immunotherapies tested in the clinic to date have focused on reestablishing self-tolerance within the T cell compartment. Monoclonal antibodies (Ab) targeting a variety of lymphocyte surface proteins have demonstrated benefits in preclinical and clinical settings. Indeed, the use of Ab to target T cells directly or indirectly has proven to be an effective strategy to rapidly suppress b cell autoimmunity and establish tissue-specific, long-term tolerance in rodent T1D models. In this review, we describe a number of these Ab-based immunotherapies, discuss associated immune regulatory mechanisms, and highlight results obtained in T1D clinical trials.

show abstract

Adaptive TGF-β-dependent regulatory T cells control autoimmune diabetes and are a privileged target of anti-CD3 antibody treatment

Cited by 163 publications

References 52 publications

Anti–IL-7 receptor-α reverses established type 1 diabetes in nonobese diabetic mice by modulating effector T-cell function

Anti–IL-7 receptor-α reverses established type 1 diabetes in nonobese diabetic mice by modulating effector T-cell function

Gut microbial markers are associated with diabetes onset, regulatory imbalance, and IFN-γ level in NOD Mice

Reestablishing T Cell Tolerance by Antibody-Based Therapy in Type 1 Diabetes

Contact Info

Product

Resources

About