scholarly journals The Role of T Cells in Type 1 Diabetes

10.5772/22040 ◽  
2011 ◽  
Author(s):  
David Wagner
Keyword(s):  
T Cells ◽  
Type 1 Diabetes

scholarly journals IL-10 Deficiency Accelerates Type 1 Diabetes Development via Modulation of Innate and Adaptive Immune Cells and Gut Microbiota in BDC2.5 NOD Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Juan Huang ◽  
Qiyuan Tan ◽  
Ningwen Tai ◽  
James Alexander Pearson ◽  
Yangyang Li ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
T Cell ◽  
Gut Microbiota ◽  
Spontaneous Diabetes ◽  
Nod Mice ◽  
Treg Cells ◽  
Diabetes Development

Type 1 diabetes is an autoimmune disease caused by T cell-mediated destruction of insulin-producing β cells. BDC2.5 T cells in BDC2.5 CD4+ T cell receptor transgenic Non-Obese Diabetic (NOD) mice (BDC2.5+ NOD mice) can abruptly invade the pancreatic islets resulting in severe insulitis that progresses rapidly but rarely leads to spontaneous diabetes. This prevention of diabetes is mediated by T regulatory (Treg) cells in these mice. In this study, we investigated the role of interleukin 10 (IL-10) in the inhibition of diabetes in BDC2.5+ NOD mice by generating Il-10-deficient BDC2.5+ NOD mice (BDC2.5+Il-10-/- NOD mice). Our results showed that BDC2.5+Il-10-/- NOD mice displayed robust and accelerated diabetes development. Il-10 deficiency in BDC2.5+ NOD mice promoted the generation of neutrophils in the bone marrow and increased the proportions of neutrophils in the periphery (blood, spleen, and islets), accompanied by altered intestinal immunity and gut microbiota composition. In vitro studies showed that the gut microbiota from BDC2.5+Il-10-/- NOD mice can expand neutrophil populations. Moreover, in vivo studies demonstrated that the depletion of endogenous gut microbiota by antibiotic treatment decreased the proportion of neutrophils. Although Il-10 deficiency in BDC2.5+ NOD mice had no obvious effects on the proportion and function of Treg cells, it affected the immune response and activation of CD4+ T cells. Moreover, the pathogenicity of CD4+ T cells was much increased, and this significantly accelerated the development of diabetes when these CD4+ T cells were transferred into immune-deficient NOD mice. Our study provides novel insights into the role of IL-10 in the modulation of neutrophils and CD4+ T cells in BDC2.5+ NOD mice, and suggests important crosstalk between gut microbiota and neutrophils in type 1 diabetes development.

scholarly journals Myeloid - derived suppressor cells in Type 1 diabetes are an expanded population exhibiting diverse T-cell suppressor mechanisms

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242092
Author(s):  
Anna Grohová ◽  
Klára Dáňová ◽  
Irena Adkins ◽  
Zdeněk Šumník ◽  
Lenka Petruželková ◽  
...  
Keyword(s):  
At Risk ◽  
T Cells ◽  
Type 1 Diabetes ◽  
Autoimmune Diseases ◽  
Suppressor Cells ◽  
Cell Contact ◽  
Myeloid Derived Suppressor Cells ◽  
Healthy Donors

Myeloid-derived suppressor cells (MDSC) represent a heterogeneous group of immature myeloid cells with immunoregulatory function in cancer and autoimmune diseases. In humans, two subsets of MDSC were determined based on the characteristic surface markers, monocytic MDSC (M-MDSC) and granulocytic MDSC (G-MDSC). Expansion of MDSC has been reported in some murine models and patients with autoimmune diseases and their immune-suppressive properties were characterized. However, the exact role of MDSC in the pathogenesis of autoimmune diseases is more complex and/or controversial. In type 1 diabetes mellitus (T1D), the increased frequency of MDSC was found in the blood of T1D patients but their suppressor capacity was diminished. In our study, we assessed the role of M-MDSC in the pathogenesis of T1D and showed for the first time the increased frequency of M-MDSC not only in the blood of T1D patients but also in their at-risk relatives compared to healthy donors. T1D patients with inadequate long term metabolic control showed an elevation of M-MDSC compared to patients with better disease control. Furthermore, we described the positive correlation between the percentage of M-MDSC and Th17 cells and IFN-γ producing T cells in T1D patients and their at-risk relatives. Finally, we found that the ability of M-MDSC to suppress autologous T cells is efficient only at the high MDSC: T cells ratio and dependent on cell-cell-contact and TGF-β production. Our data show that the engagement of MDSC in the pathogenesis of T1D is evident, yet not entirely explored and more experiments are required to clarify whether MDSC are beneficial or harmful in T1D.

scholarly journals New Insights Into the Role of Autoreactive CD8 T Cells and Cytokines in Human Type 1 Diabetes

2021 ◽  
Vol 11 ◽  
Author(s):  
Christine Bender ◽  
Sakthi Rajendran ◽  
Matthias G. von Herrath
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Beta Cell ◽  
Cd8 T Cells ◽  
Over Expression ◽  
Cell Dysfunction ◽  
Human Type ◽  
Human Type 1 Diabetes

Since the establishment of the network for pancreatic organ donors with diabetes (nPOD), we have gained unprecedented insight into the pathology of human type 1 diabetes. Many of the pre-existing “dogmas”, mostly derived from studies of animal models and sometimes limited human samples, have to be revised now. For example, we have learned that autoreactive CD8 T cells are present even in healthy individuals within the exocrine pancreas. Furthermore, their “attraction” to islets probably relies on beta-cell intrinsic events, such as the over-expression of MHC class I and resulting presentation of autoantigens such as (prepro)insulin. In addition, we are discovering other signs of beta-cell dysfunction, possibly at least in part due to stress, such as the over-expression of certain cytokines. This review summarizes the latest developments focusing on cytokines and autoreactive CD8 T cells in human type 1 diabetes pathogenesis.

scholarly journals NKG2D signaling within the pancreatic islets reduces NOD diabetes and increases protective central memory CD8+ T cell numbers

2020 ◽  
Author(s):  
Ada Admin ◽  
Andrew P. Trembath ◽  
Kelsey L. Krausz ◽  
Neekun Sharma ◽  
Ivan C. Gerling ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
T Cell ◽  
Autoimmune Diabetes ◽  
Central Memory ◽  
Anatomical Location

NKG2D is implicated in autoimmune diabetes. However, the role of this receptor in diabetes pathogenesis is unclear owing to conflicting results with studies involving global inhibition of NKG2D signaling. We found that NKG2D and its ligands are present in human pancreata, with expression of NKG2D and its ligands increased in the islets of patients with type 1 diabetes. To directly assess the role of NKG2D in the pancreas, we generated NOD mice that express an NKG2D ligand in b-islet cells. Diabetes was reduced in these mice. The reduction corresponded with a decrease in the effector to central memory CD8<sup>+</sup> T cell ratio. Further, NKG2D signaling during in vitro activation of both mouse and human CD8+ T cells resulted in an increased number of central memory CD8<sup>+</sup> T cells and diabetes protection by central memory CD8<sup>+</sup> T cells in vivo. Taken together, these studies demonstrate that there is a protective role for central memory CD8<sup>+</sup> T cells in autoimmune diabetes and that this protection is enhanced with NKG2D signaling. These findings stress the importance of anatomical location when determining the role NKG2D signaling plays, as well as when developing therapeutic strategies targeting this pathway, in type 1 diabetes development.

scholarly journals The role of regulatory T cells in type 1 diabetes

2021 ◽  
pp. 0
Author(s):  
Margarida Vieira ◽  
Celestino Neves ◽  
João Neves ◽  
Davide Carvalho
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Regulatory T Cells

scholarly journals NKG2D signaling within the pancreatic islets reduces NOD diabetes and increases protective central memory CD8+ T cell numbers

2020 ◽  
Author(s):  
Ada Admin ◽  
Andrew P. Trembath ◽  
Kelsey L. Krausz ◽  
Neekun Sharma ◽  
Ivan C. Gerling ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
T Cell ◽  
Autoimmune Diabetes ◽  
Central Memory ◽  
Anatomical Location

NKG2D is implicated in autoimmune diabetes. However, the role of this receptor in diabetes pathogenesis is unclear owing to conflicting results with studies involving global inhibition of NKG2D signaling. We found that NKG2D and its ligands are present in human pancreata, with expression of NKG2D and its ligands increased in the islets of patients with type 1 diabetes. To directly assess the role of NKG2D in the pancreas, we generated NOD mice that express an NKG2D ligand in b-islet cells. Diabetes was reduced in these mice. The reduction corresponded with a decrease in the effector to central memory CD8<sup>+</sup> T cell ratio. Further, NKG2D signaling during in vitro activation of both mouse and human CD8+ T cells resulted in an increased number of central memory CD8<sup>+</sup> T cells and diabetes protection by central memory CD8<sup>+</sup> T cells in vivo. Taken together, these studies demonstrate that there is a protective role for central memory CD8<sup>+</sup> T cells in autoimmune diabetes and that this protection is enhanced with NKG2D signaling. These findings stress the importance of anatomical location when determining the role NKG2D signaling plays, as well as when developing therapeutic strategies targeting this pathway, in type 1 diabetes development.

Role of Regulatory Invariant CD1d-Restricted Natural Killer T-Cells in Protection Against Type 1 Diabetes

2005 ◽  
Vol 31 (3) ◽  
pp. 177-188 ◽  
Author(s):  
Shabbir Hussain ◽  
Melany Wagner ◽  
Dalam Ly ◽  
Terry L. Delovitch
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Natural Killer ◽  
Natural Killer T Cells ◽  
Killer T Cells ◽  
Natural Killer T

scholarly journals Visualizing the Role of Cbl-b in Control of Islet-Reactive CD4 T Cells and Susceptibility to Type 1 Diabetes

2011 ◽  
Vol 186 (4) ◽  
pp. 2024-2032 ◽  
Author(s):  
Gerard F. Hoyne ◽  
Eleanor Flening ◽  
Mehmet Yabas ◽  
Charis Teh ◽  
John A. Altin ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Cd4 T Cells
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