scholarly journals Regulatory T cells control Effector T cell Inflammation in Human Prediabetes

2022 ◽  
Author(s):  
Rui Liu ◽  
Gabriella H. Pugh ◽  
Erin Tevonian ◽  
Katherine Thompson ◽  
Douglas A. Lauffenburger ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Mitochondrial Function ◽  
Cytokine Production ◽  
Serum Markers ◽  
Inflammatory State ◽  
Lipid Metabolism Genes

A disparate array of plasma/serum markers provide evidence for chronic inflammation in human prediabetes, a condition that is most closely replicated by standard mouse models of obesity and meta-flammation. These remain largely non-actionable, and contrast with our rich understanding of inflammation in human type 2 diabetes. New data show that<b> </b>inflammatory profiles produced by CD4<sup>+</sup> T cells define human prediabetes as a unique inflammatory state. Regulatory T cells (Tregs) control mitochondrial function and cytokine production by CD4<sup>+</sup> effector T cells (Teff) in prediabetes and type 2 diabetes by supporting Th17 or Th1 cytokine production, respectively. These data suggest that Treg control of Teff metabolism controls inflammation differentially in prediabetes compared to type 2 diabetes. Queries of genes that impact mitochondrial function and/or pathways leading to transcription of lipid metabolism genes identified the fatty acid importer CD36 as highly expressed in Tregs but not Teff from prediabetes subjects. Pharmacological blockade of CD36 in Tregs from prediabetes subjects decreased Teff production of the Th17 cytokines that differentiate overall prediabetes inflammation. We conclude Tregs control CD4<sup>+</sup> T cell cytokine profiles through mechanisms determined, at least in part, by host metabolic status. Furthermore, Treg CD36 uniquely promotes Th17 cytokine production by Teff in prediabetes.

scholarly journals Mechanism of Reduced T-Cell Effector Functions and Class-Switched Antibody Responses to Herpes Simplex Virus Type 2 in the Absence of B7 Costimulation

2003 ◽  
Vol 77 (4) ◽  
pp. 2426-2435 ◽  
Author(s):  
Lydia G. Thebeau ◽  
Lynda A. Morrison
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytokine Production ◽  
Antibody Responses ◽  
Wild Type ◽  
Effector Functions ◽  
Lymphocyte Activity ◽  
Ifn Γ ◽  
Simplex Virus

ABSTRACT T-cell costimulation molecules B7-1 and B7-2 play an important role in activation of T cells to cytolytic effector function and production of cytokines. Interaction with B7 also causes T cells to upregulate surface molecules, such as CD40L, that effectively stimulate antibody responses in conjunction with cytokines. We have shown that mice lacking both B7-1 and B7-2 (B7KO mice), when infected intravaginally with virulent herpes simplex virus type 2 (HSV-2), developed more severe disease and higher mortality than their wild-type counterparts. We have now investigated the effects of B7 costimulation deficiency on induction of immune responses to HSV-2 infection of the genital tract. Fewer gamma interferon (IFN-γ)-producing T cells were present in the genital lymph nodes of B7KO mice compared to wild-type mice, either acutely after primary infection or in recall responses. Less IFN-γ and especially interleukin-10 were produced by B7KO mice, and cytolytic T-lymphocyte activity was also attenuated. Reduced expression of CD25 on CD4+ T cells after infection of B7KO mice was consistent with deficits in T-cell activation to effector functions. Although HSV-specific immunoglobulin M (IgM) titers were comparable for both B7KO mice and wild-type mice, B7KO mice had significant deficits in HSV-specific serum IgG responses, with markedly reduced levels of IgG2a and IgG1. In addition, significantly less IgG was detected in the vaginal secretions of B7KO mice than in those from wild-type mice. CD4+ T-cell expression of CD40L was depressed in B7KO mice in vivo and in vitro. Together with reduced cytokine production, these results suggest a mechanism for decreased IgG class switching or production. Thus, in the absence of B7 costimulation, naïve T cells fail to undergo proper activation in response to HSV-2, which limits T-cell cytokine production, cytotoxic T lymphocyte activity, and provision of help for class-switched antibody responses.

scholarly journals Attenuation of CD4 + CD25 + Regulatory T Cells in the Tumor Microenvironment by Metformin, a Type 2 Diabetes Drug

EBioMedicine ◽  
2017 ◽  
Vol 25 ◽  
pp. 154-164 ◽  
Author(s):  
Yuki Kunisada ◽  
Shingo Eikawa ◽  
Nahoko Tomonobu ◽  
Shohei Domae ◽  
Takenori Uehara ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Regulatory T Cells ◽  
Diabetes Drug

scholarly journals Parasite Proximity Drives the Expansion of Regulatory T Cells in Peyer's Patches following Intestinal Helminth Infection

2015 ◽  
Vol 83 (9) ◽  
pp. 3657-3665 ◽  
Author(s):  
Ilaria Mosconi ◽  
Lalit Kumar Dubey ◽  
Beatrice Volpe ◽  
Julia Esser-von Bieren ◽  
Mario M. Zaiss ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Cytokine Production ◽  
Helminth Infection ◽  
Peyer's Patches ◽  
Intestinal Helminth ◽  
Peyer’S Patches ◽  
Intestinal Helminths ◽  
Content Type

Helminth infections are typically chronic in nature; however, the exact molecular mechanisms by which these parasites promote or thwart host immunity remain unclear. Worm expulsion requires the differentiation of CD4+T cells into Th2 cells, while regulatory T cells (Tregs) act to dampen the extent of the Th2 response. Priming of T cells requires drainage or capture of antigens within lymphoid tissues, and in the case of intestinal helminths, such sites include the mucosa-associated Peyer's patches (PPs) and the draining mesenteric lymph nodes (MLN). To gain insight into when and where the activation of the adaptive T cell response takes place following intestinal helminth infection, we analyzed Th2 and Treg responses in the PPs and MLN following infection with the murine intestinal helminthHeligmosomoides polygyrusbakeri. Protective Th2 responses were observed to be largely restricted to the MLN, while a greater expansion of Tregs occurred within the PPs. Interestingly, those PPs that formed a contact with the parasite showed the greatest degree of Treg expansion and no evidence of type 2 cytokine production, indicating that the parasite may secrete products that act in a local manner to selectively promote Treg expansion. This view was supported by the finding thatH. polygyrusbakerilarvae could promote Treg proliferationin vitro. Taken together, these data indicate that different degrees of Treg expansion and type 2 cytokine production occur within the PPs and MLN following infection with the intestinal helminthH. polygyrusbakeriand indicate that these organs exhibit differential responses following infection with intestinal helminths.

scholarly journals Activation of bone marrow adaptive immunity in type 2 diabetes: rescue by co-stimulation modulator Abatacept

2020 ◽  
Author(s):  
Marianna Santopaolo ◽  
Niall Sullivan ◽  
Anita C. Thomas ◽  
Valeria Alvino ◽  
Lindsay Nicholson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Insulin Sensitivity ◽  
Adaptive Immunity ◽  
Low Grade ◽  
Immune Profile ◽  
Adaptive Immune

AbstractHypothesisType 2 diabetes (T2D) is characterized by low-grade inflammation. Here, we investigated the state of adaptive immunity in bone marrow (BM) of patients and mice with T2D. We also tested if inhibition T cell co-stimulation by Abatacept could rescue the immune profile of T2D mice.MethodsFlow-cytometry and cytokine analyses were performed on BM samples from patients with or without T2D. Moreover, we studied the immune profile of db/db and control wt/db mice. A cohort of db/db mice was randomized to receive Abatacept or vehicle for 4 weeks, with endpoints being immune cell profile and indexes of insulin sensitivity and heart performance.ResultsT2D patients showed increased frequencies of BM CD4+ (2.8-fold, p=0.001) and CD8+ T cells (1.8-fold, p=0.01), with upregulation of the activation marker CD69 and homing receptor CCR7 in CD4+ (1.64-fold, p=0.003 and 2.27-fold, p=0.01, respectively) and CD8+ fractions (1.79-fold, p=0.05 and 1.69-fold, p=0.02, respectively). CCL19 (CCR7 receptor ligand) and CXCL10/11 (CXCR3 receptor ligands), implicated in T cell migration and activation, were the most differentially modulated chemokines. Studies in mice confirmed the activation of adaptive immunity in T2D. Abatacept reduced the activation of T cells and levels of pro-inflammatory chemokines and cytokines. Additionally, Abatacept improved indexes of cardiac systolic function, but not insulin sensitivity.ConclusionsThese novel findings support the concept of BM adaptive immune activation in T2D. Modulation of T cell co-stimulation could represent an attractive and immediately available modality to dampen inappropriate activation of adaptive immune response and protect from target organ damage.

scholarly journals Elevated circulating effector memory T cells but similar levels of regulatory T cells in patients with type 2 diabetes mellitus and cardiovascular disease

2018 ◽  
Vol 16 (3) ◽  
pp. 270-280 ◽  
Author(s):  
Sara Rattik ◽  
Daniel Engelbertsen ◽  
Maria Wigren ◽  
Irena Ljungcrantz ◽  
Gerd Östling ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
T Cells ◽  
Type 2 Diabetes Mellitus ◽  
Regulatory T Cells ◽  
Memory T Cells ◽  
Effector Memory ◽  
Effector Memory T Cells

Type 2 diabetes mellitus is associated with an elevated risk of cardiovascular disease, but the mechanism through which diabetes contributes to cardiovascular disease development remains incompletely understood. In this study, we compared the association of circulating regulatory T cells, naïve T cells, effector memory T cells or central memory T cells with cardiovascular disease in patients with and without type 2 diabetes mellitus. Percentage of circulating T cell subsets was analysed by flow cytometry in type 2 diabetes mellitus subjects with and without prevalent cardiovascular disease as well as in non-diabetic subjects with and without prevalent cardiovascular disease from the Malmö SUMMIT cohort. Subjects with type 2 diabetes mellitus had elevated percentages of effector memory T cells (CD4+CD45RO+CD62L–; 21.8% ± 11.2% vs 17.0% ± 9.2% in non-type 2 diabetes mellitus, p < 0.01) and central memory T cells (CD4+CD45RO+CD62L+; 38.0% ± 10.7% vs 36.0% ± 9.5% in non-type 2 diabetes mellitus, p < 0.01). In contrast, the frequency of naïve T cells was reduced (CD4+CD45RO–CD62L+, 35.0% ± 16.5% vs 42.9% ± 14.4% in non-type 2 diabetes mellitus, p < 0.001). The proportion of effector memory T cells was increased in type 2 diabetes mellitus subjects with cardiovascular disease as compared to those without (26.4% ± 11.5% vs 18.4% ± 10.2%, p < 0.05), while no difference in regulatory T cells was observed between these two patient groups. This study identifies effector memory T cells as a potential cellular biomarker for cardiovascular disease among subjects with type 2 diabetes mellitus, suggesting a state of exacerbated immune activation in type 2 diabetes mellitus patients with cardiovascular disease.

scholarly journals Th17 and regulatory T cells in patients with different time of progression of type 2 diabetes mellitus

2020 ◽  
Vol 45 (1) ◽  
pp. 29-36 ◽  
Author(s):  
Juan Guzmán-Flores ◽  
Joel Ramírez-Emiliano ◽  
Victoriano Pérez-Vázquez ◽  
Sergio López-Briones
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
T Cells ◽  
Type 2 Diabetes Mellitus ◽  
Regulatory T Cells

Tregs in fibrosis: To know your enemy, you must become your enemy

2019 ◽  
Vol 4 (39) ◽  
pp. eaay1160 ◽  
Author(s):  
Suzanne M. Bal ◽  
Ralph Stadhouders
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Cytokine Production ◽  
T Helper ◽  
Related Research ◽  
T Helper 2 ◽  
Link Type ◽  
Research Article

T helper 2–skewed regulatory T cells in the skin use GATA3 to suppress local profibrotic type 2 cytokine production. See the related Research Article by Kalekar et al.

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