scholarly journals Siplizumab selectively depletes effector memory T-cells and promotes a relative expansion of alloreactive regulatory T-cells in vitro

immuneACCESS ◽  
2019 ◽  
Author(s):  
MA Podestà ◽  
C van Binder ◽  
F Sellberg ◽  
S DeWolf ◽  
B Shonts ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Memory T Cells ◽  
Effector Memory ◽  
Effector Memory T Cells ◽  
Relative Expansion

scholarly journals Siplizumab selectively depletes effector memory T cells and promotes a relative expansion of alloreactive regulatory T cells in vitro

2019 ◽  
Vol 20 (1) ◽  
pp. 88-100 ◽  
Author(s):  
Manuel A. Podestà ◽  
Christian Binder ◽  
Felix Sellberg ◽  
Susan DeWolf ◽  
Brittany Shonts ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Memory T Cells ◽  
Effector Memory ◽  
Effector Memory T Cells ◽  
Relative Expansion

Abstract 561: GITR Activation Promotes Regulatory CD4+ T-cell Responses and Stimulates Leukocyte Recruitment in Atherosclerotic Plaques

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Annelie Shami ◽  
Svenja Meiler ◽  
Holger Winkels ◽  
Norbert Gerdes ◽  
Esther Lutgens
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
Regulatory T Cells ◽  
B Cell ◽  
Memory T Cells ◽  
Effector Memory ◽  
Wild Type ◽  
Atherosclerotic Lesions ◽  
Effector Memory T Cells ◽  
Antigen Presenting

Glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR) - a costimulatory molecule - is expressed on CD4(+) effector memory T cells and regulatory T cells as well as antigen-presenting cells and mast cells; while its ligand (GITRL) is mainly found on antigen-presenting cells and endothelial cells. However, the definitive role of GITR in atherosclerosis is not fully understood. Our hypothesis is that signaling through GITR plays a vital role in atherosclerosis progression. Low-density lipoprotein receptor-deficient mice (Ldlr -/- ) with B-cell-restricted overexpression of GITRL ( Gitrl tg ) fed a high-cholesterol diet showed a profound increase in both CD4(+) effector memory T cells and regulatory T cells in secondary lymphoid organs in comparison to wild-type controls. Additionally, the number of regulatory T cells was significantly enhanced in the thymus and aorta of these mice along with increased GITRL and interleukin-2 transcript levels. Atherosclerotic lesions of Ldlr -/- Gitrl tg mice contained more total CD3 + T cells as well as Foxp3 + regulatory T cells overall, leading to significantly less severe atherosclerosis. Conversely, atherosclerosis was found to be less severe in mice deficient in apolipoprotein E and GITR (ApoE -/- GITR -/- ). Atherosclerotic lesions in these mice were found to contain less macrophages and CD3-positive T-cells. Perfusion assays using two-photon excitation microscopy revealed less wild type leukocyte adhesion on GITR-deficient endothelium, with a further reduction in adhesion by GITR-deficient leukocytes to both wild type and GITR-deficient endothelia. Finally, expression of GITR expression in human plaque tissue was significantly increased in ruptured plaques. In conclusion, these data indicate that continuous GITR stimulation through B cell GITRL acts protective in a mouse model of atherosclerosis by regulating the balance between regulatory and effector memory CD4(+) T cells, while GITR activation on endothelial cells promotes atherogenesis by stimulating leukocyte recruitment into the plaque.

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 α 4 β 7 + CD4 + Effector/Effector Memory T Cells Differentiate into Productively and Latently Infected Central Memory T Cells by Transforming Growth Factor β1 during HIV-1 Infection

2018 ◽  
Vol 92 (8) ◽  
Author(s):  
Ka-Wai Cheung ◽  
Tongjin Wu ◽  
Sai Fan Ho ◽  
Yik Chun Wong ◽  
Li Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Transforming Growth Factor ◽  
Memory T Cells ◽  
Central Memory ◽  
Effector Memory ◽  
Effector Memory T Cells ◽  
Latently Infected ◽  
Hiv 1

ABSTRACT HIV-1 transmission occurs mainly through mucosal tissues. During mucosal transmission, HIV-1 preferentially infects α 4 β 7 + gut-homing CCR7 − CD4 + effector/effector memory T cells (T EM ) and results in massive depletion of these cells and other subsets of T EM in gut-associated lymphoid tissues. However, besides being eliminated by HIV-1, the role of T EM during the early stage of infection remains inconclusive. Here, using in vitro -induced α 4 β 7 + gut-homing T EM (α 4 β 7 + T EM ), we found that α 4 β 7 + T EM differentiated into CCR7 + CD4 + central memory T cells (T CM ). This differentiation was HIV-1 independent but was inhibited by SB431542, a specific transforming growth factor β (TGF-β) receptor I kinase inhibitor. Consistently, T EM -to-T CM differentiation was observed in α 4 β 7 + T EM stimulated with TGF-β1 (TGF-β). The T CM properties of the TGF-β-induced T EM -derived T CM (α 4 β 7 + T CM ) were confirmed by their enhanced CCL19 chemotaxis and the downregulation of surface CCR7 upon T cell activation in vitro . Importantly, the effect of TGF-β on T CM differentiation also held in T EM directly isolated from peripheral blood. To investigate the significance of the TGF-β-dependent T EM -to-T CM differentiation in HIV/AIDS pathogenesis, we observed that both productively and latently infected α 4 β 7 + T CM could differentiate from α 4 β 7 + T EM in the presence of TGF-β during HIV-1 infection. Collectively, this study not only provides a new insight for the plasticity of T EM but also suggests that the TGF-β-dependent T EM -to-T CM differentiation is a previously unrecognized mechanism for the formation of latently infected T CM after HIV-1 infection. IMPORTANCE HIV-1 is the causative agent of HIV/AIDS, which has led to millions of deaths in the past 30 years. Although the implementation of highly active antiretroviral therapy has remarkably reduced the HIV-1-related morbidity and mortality, HIV-1 is not eradicated in treated patients due to the presence of latent reservoirs. Besides, the pathogenesis in CD4 T cells early after infection still remains elusive. Immediately after HIV-1 mucosal infection, CD4 T cells are preferentially infected and depleted. However, in addition to being depleted, the other roles of the CD4 T cells, especially the effector/effector memory T cells (T EM ), in disease progression are not completely understood. The significance of this study is in revealing a novel mechanism for the formation of latently HIV-1-infected central memory CD4 T cells, a major latent reservoir from CD4 T EM after infection. Our findings suggest previously unrecognized roles of CD4 T EM in HIV-1 pathogenesis.

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