scholarly journals Sociodemographic effects on immune cell composition in a free-ranging non-human primate

2021 ◽  
Author(s):  
Mitchell R. Sanchez Rosado ◽  
Nicole Marzan-Rivera ◽  
Marina M. Watowich ◽  
Petraleigh Pantoja ◽  
Melissa A. Pavez-Fox ◽  
...  
Keyword(s):  
T Regulatory Cells ◽  
Immune Cell ◽  
Rhesus Macaques ◽  
Older Individuals ◽  
Regulatory Cells ◽  
Primate Model ◽  
Cell Ratio ◽  
Age Related ◽  
Hla Dr ◽  
Social Adversity

AbstractAging results in declines in immune function and increases in inflammation, which underlie many age-related diseases. These immunosenescent signatures are similar to those seen in individuals exposed to social adversity, who may age more rapidly than those unexposed. Yet, it is unclear how social adversity alters immunity across demographic factors - data that are essential to identify how it might increase aging-related diseases. Here, we investigated how age, sex, and social adversity predicted immune cell proportions in 250 rhesus macaques living in a semi-naturalistic colony. As macaques aged, they exhibited signatures of immunosenescence. Older individuals had signatures of diminished antibody production and adaptive immunity, with declines in CD20+ B cells, CD20+/CD3+ cell ratio, and the CD4+/CD8+ T cell ratio. At all ages, females had higher CD20+/CD3+ and CD4+/CD8+ ratios, indicative of a stronger antibody and adaptive immune response that may facilitate pathogen clearance even with increasing age. Older individuals had signatures of inflammation, with higher proportions of CD3+/CD8+ Cytotoxic T cells, CD16+/CD3- Natural Killer cells, CD3+/CD4+/CD25+ and CD3+/CD8+/CD25+ T regulatory cells, and CD14+/CD16+/HLA-DR+ intermediate monocytes, combined with lower levels of CD14+/CD16-/HLA-DR+ classical monocytes. Notably, we found an interaction between age and social adversity, where low-status individuals had higher proportions of CD3+/CD4+/CD25+ T regulatory cells for their age, compared to higher-status individuals. Together, our study identifies immune cell types that are affected by age and sex in the premier nonhuman primate model of human biology and behavior, and demonstrate a novel link between inflammatory CD4+ T regulatory cells and social adversity.

scholarly journals Effects of Age and Social Adversity on Immune Cell Populations in a Non-Human Primate Model of Human Aging

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 532-533
Author(s):  
Mitchell Sanchez-Rosado ◽  
Noah Snyder-Mackler ◽  
James Higham ◽  
Lauren Brent ◽  
Nicole Marzan-Rivera ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immune Function ◽  
Immune Cell ◽  
Rhesus Macaques ◽  
Older Individuals ◽  
Primate Model ◽  
Hla Dr ◽  
Social Adversity ◽  
Classical Monocytes

Abstract Significant hallmarks of aging are immune function decline and rising cumulative inflammation. These immunosenescent signatures are also found in individuals who experience chronic social adversity, independently of age. However, no studies to date have examined how social adversity alters immune function across the lifespan –data that are essential to identify the molecular routes through which social adversity might lead to increased aging-related disease. Over a two-year period, we investigated how age and social adversity (quantified by low social status) affected immunity. We measured immune cell proportions at baseline and their gene regulation after in vitro stimulation with pathogen molecules that stimulated both Th1 and Th2 immune responses in a population of free-ranging rhesus macaques. We first performed flow cytometry on peripheral whole blood to quantify changes on immune cell proportions across the lifespan (n=235) and in animals of different social statuses (n=141). We found significant decreases in CD20+ B cells and CD3+/CD4+ T cell proportions with age, suggesting diminished antibody production and adaptive immune responses in older individuals. Age-associated increases in CD3+/CD8+, CD3+/CD4+/CD25+ T regulatory cells and CD14-/CD16+/HLA-DR+ non-classical monocytes indicated heightened baseline inflammation in older animals. Social adversity recapitulated the effects of aging in CD14+/CD16-/HLA-DR+ classical monocytes, indicating immune deficits in phagocytosis and pathogen clearance in older and lower status individuals. Using RNA-seq, our stimulations (n=1,320) will allow us to identify molecular immune pathways that are disrupted by age and social adversity, similarities in response between age and adversity, and how the effect of adversity varies across the lifespan.

scholarly journals Social Adversity Impacts on the Rhesus Macaque Immune System Resemble Those of Aging

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 925-925
Author(s):  
Mitchell Sanchez-Rosado ◽  
Noah Snyder-Mackler ◽  
Lauren Brent ◽  
James Higham ◽  
Clare Kimock ◽  
...  
Keyword(s):  
Immune System ◽  
T Cell ◽  
Social Status ◽  
Immune Cell ◽  
Rhesus Macaques ◽  
Natural Aging ◽  
High Status ◽  
Regulatory Cells ◽  
T Regulatory Cell ◽  
Social Adversity

Abstract Social adversity can impact immune function and is associated with increased morbidity and mortality. Many of these immune-related changes resemble the effects of the natural aging process. To date, little is known about the effects of social adversity on the immune system change across the lifetime. Here, we investigated how aging and social adversity (measured as social status) impact immune cell proportions. We performed flow cytometry on peripheral whole blood from a population of free-ranging rhesus macaques to quantify changes on immune cell proportions across the lifespan (n=99) and across different social statuses (n=53). Overall, we found that high adversity recapitulated the effects of aging. We found significant shared decreases in CD3+/CD4+ T cell proportions and corresponding increases in CD3+/CD8+ T cell proportions between individuals of older ages and low social status. These findings suggest that social adversity has similar effects to aging on T cell proportions, possibly affecting the T cell component of the immune response. In contrast, CD3+/CD4+/CD25+ T regulatory cell proportions increased with age, which is typical of normal aging. Contrary to our expectations, these cells were less abundant in low status individuals, indicating some overall regulatory immune deficits specific to lower status individuals. CD3+/CD8+/CD25+ T regulatory cells, which contribute to self-tolerance, were higher in high status individuals, suggesting that overall primary immune regulatory cells can be affected by social adversity and impair the regulation of inflammation. We provide evidence that social adversity alters immune cell proportions, implicating it in the development of inflammatory and/or aging-related diseases.

scholarly journals Differentiation of type 1 T regulatory cells (Tr1) by tolerogenic DC-10 requires the IL-10–dependent ILT4/HLA-G pathway

Blood ◽  
2010 ◽  
Vol 116 (6) ◽  
pp. 935-944 ◽  
Author(s):  
Silvia Gregori ◽  
Daniela Tomasoni ◽  
Valentina Pacciani ◽  
Miriam Scirpoli ◽  
Manuela Battaglia ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
T Regulatory Cells ◽  
Interleukin 10 ◽  
Regulatory Cells ◽  
Hla Dr ◽  
Human Dendritic Cells ◽  
Tr1 Cells

Abstract Type 1 T regulatory (Tr1) cells suppress immune responses in vivo and in vitro and play a key role in maintaining tolerance to self- and non–self-antigens. Interleukin-10 (IL-10) is the crucial driving factor for Tr1 cell differentiation, but the molecular mechanisms underlying this induction remain unknown. We identified and characterized a subset of IL-10–producing human dendritic cells (DCs), termed DC-10, which are present in vivo and can be induced in vitro in the presence of IL-10. DC-10 are CD14+, CD16+, CD11c+, CD11b+, HLA-DR+, CD83+, CD1a−, CD1c−, express the Ig-like transcripts (ILTs) ILT2, ILT3, ILT4, and HLA-G antigen, display high levels of CD40 and CD86, and up-regulate CD80 after differentiation in vitro. DC-10 isolated from peripheral blood or generated in vitro are potent inducers of antigen-specific IL-10–producing Tr1 cells. Induction of Tr1 cells by DC-10 is IL-10–dependent and requires the ILT4/HLA-G signaling pathway. Our data indicate that DC-10 represents a novel subset of tolerogenic DCs, which secrete high levels of IL-10, express ILT4 and HLA-G, and have the specific function to induce Tr1 cells.

scholarly journals Tregs and GvHD prevention by extracorporeal photopheresis: observations from a clinical trial

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Crocchiolo Roberto ◽  
Cesana Clara ◽  
Girgenti Debora ◽  
Bertani Giambattista ◽  
Barba Claudia ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Longitudinal Data ◽  
Graft Versus Host Disease ◽  
T Regulatory Cells ◽  
Chronic Gvhd ◽  
Extracorporeal Photopheresis ◽  
Regulatory Cells ◽  
Graft Versus Host ◽  
Hla Dr ◽  
Potential Biomarker

AbstractThe aim of the present study was to evaluate the circulating T regulatory cells (Tregs) in patients undergoing extracorporeal photopheresis (ECP) for the prevention of chronic graft-versus-host disease (GvHD) and to search for any correlation between Tregs counts and chronic GvHD occurrence. Among n = 12 patients with complete longitudinal data, the median cumulative values of absolute peripheral Tregs counts were 21.64 and 63.49 cells/µL for patients who developed chronic GvHD and those who did not develop it, respectively (p = 0.05). The analysis of the median absolute counts of peripheral HLA-DR + Tregs provided similar results, showing that 20% (1 out of 5) and 100% (7 out of 7) of patients with HLA-DR + Tregs values of > 5 cells/µL were in the GvHD and non-GvHD groups, respectively (p = 0.01). In conclusion, the present results support the involvement of Tregs in the prevention of chronic GvHD in patients receiving ECP and suggest Tregs count as a potential biomarker of ECP effectiveness. Future strategies are needed to enhance Tregs expansion and/or activity in conjunction with ECP for an effective chronic GvHD prevention.

scholarly journals Immunopathology of Postprimary Tuberculosis: Increased T-Regulatory Cells and DEC-205-Positive Foamy Macrophages in Cavitary Lesions

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Kerry J. Welsh ◽  
Semyon A. Risin ◽  
Jeffrey K. Actor ◽  
Robert L. Hunter
Keyword(s):  
Endothelial Cells ◽  
T Regulatory Cells ◽  
Immune Cell ◽  
Cell Types ◽  
Cell Marker ◽  
Regulatory Cells ◽  
Immunohistochemical Studies ◽  
Mycobacterial Antigens ◽  
Foamy Macrophages ◽  
Lipid Pneumonia

Postprimary tuberculosis occurs in immunocompetent people infected withMycobacterium tuberculosis. It is restricted to the lung and accounts for 80% of cases and nearly 100% of transmission. Little is known about the immunopathology of postprimary tuberculosis due to limited availability of specimens. Tissues from 30 autopsy cases of pulmonary tuberculosis were located. Sections of characteristic lesions of caseating granulomas, lipid pneumonia, and cavitary stages of postprimary disease were selected for immunohistochemical studies of macrophages, lymphocytes, endothelial cells, and mycobacterial antigens. A higher percentage of cells in lipid pneumonia (36.1%) and cavitary lesions (27.8%) were positive for the dendritic cell marker DEC-205, compared to granulomas (9.0%,P<.05). Cavities contained significantly more T-regulatory cells (14.8%) than found in lipid pneumonia (5.2%) or granulomas (4.8%). Distribution of the immune cell types may contribute to the inability of the immune system to eradicate tuberculosis.

scholarly journals 2431

2017 ◽  
Vol 1 (S1) ◽  
pp. 37-37
Author(s):  
Andrea Lin ◽  
Clayton Mathews ◽  
Michael Haller ◽  
Todd Brusko ◽  
Mark Atkinson ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Type 1 Diabetes ◽  
T Regulatory Cells ◽  
Immune Cell ◽  
Diabetic Mouse ◽  
Regulatory Cells ◽  
Flow Cytometry Analysis ◽  
Nonobese Diabetic Mouse ◽  
Nonobese Diabetic

OBJECTIVES/SPECIFIC AIMS: Understand the immunomodulatory effects of anti-thymocyte globulin (ATG) and granulocyte colony stimulating factor (G-CSF) on type 1 diabetes patients using samples and in the preclinical model, the nonobese diabetic mouse. METHODS/STUDY POPULATION: Flow cytometry analysis of phase 1 peripheral blood samples treatment of nonobese diabetic mouse with ATG and GCSF and flow cytometry analysis of immune organs (spleen, lymph nodes, blood, bone marrow). RESULTS/ANTICIPATED RESULTS: Changes in both innate and adaptive immune cell subsets including plasmacytoid dendritic cells, naive, memory, effector CD4+ and CD8+ T-cells, and CD4+ T-regulatory cells and CD8+ T-regulatory cells DISCUSSION/SIGNIFICANCE OF IMPACT: Understanding of immune cell targets for immunotherapy in new-onset type 1 diabetes patients.

HLA-DR Expressing Peripheral T Regulatory Cells in Newly Diagnosed Patients with Different Forms of Autoimmune Thyroid Disease

Thyroid ◽  
2008 ◽  
Vol 18 (11) ◽  
pp. 1195-1200 ◽  
Author(s):  
Stelios Fountoulakis ◽  
George Vartholomatos ◽  
Nikolaos Kolaitis ◽  
Stathis Frillingos ◽  
George Philippou ◽  
...  
Keyword(s):  
Thyroid Disease ◽  
Autoimmune Thyroid Disease ◽  
T Regulatory Cells ◽  
Newly Diagnosed ◽  
Regulatory Cells ◽  
Autoimmune Thyroid ◽  
Hla Dr

scholarly journals The influence of humoral factors of homeostatistic proliferation on t-regulatory cells in vitro

2019 ◽  
Vol 18 (1) ◽  
pp. 286-293
Author(s):  
D. V. Shevyrev ◽  
E. A. Blinova ◽  
V. A. Kozlov
Keyword(s):  
T Regulatory Cells ◽  
Homeostatic Proliferation ◽  
Primary Role ◽  
Regulatory Cells ◽  
Humoral Factors ◽  
Effector Cells ◽  
Hla Dr ◽  
Healthy Donors ◽  
Cd4 Lymphocytes

Aim. The aim of this study was the investigation of the influence of humoral factors of homeostatic proliferation IL-7 and IL-15 on T-regulatory cells in healthy donors.Materials and methods. The study included 15 conditionally healthy donors. Phenotyping and evaluation of expression changes of transcription factor FoxP3 and the main functional molecules on T-regulatory cells such as PD-L1, CTLA-4 and HLA-DR during cultivation under IL-7, IL-15 and anti-CD3 stimulation combined with IL-2 were performed by flow cytometry. Also, we estimated proliferation intensity of T-regulatory cells in the course of cultivation.Results. We revealed that humoral factors of homeostatic proliferation can effectively support a pool of T-regulatory cells during cultivation by number and phenotype and can maintain expression of important molecules such as PD-L1 and HLA-DR on regulatory T-cell surface. In addition, our study showed that IL-7 and IL-15 can cause relatively low T-regulatory cells proliferation in comparison to CD4+- lymphocytes.Conclusion. The observed ability of homeostatic proliferation factors to maintain T-regulatory cells pool presumably can play an important role in lymphopenic conditions when the number of effector cells is decreased and the insufficiency of interleukin IL-2 is observed, which plays a primary role in the homeostasis of T-regulatory cells in normal conditions.

Sign in / Sign up

Export Citation Format

Share Document