scholarly journals Pregnancy-Associated Alterations of Peripheral Blood Immune Cell Numbers in Domestic Sows Are Modified by Social Rank

Animals ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 112
Author(s):  
Christiane Schalk ◽  
Birgit Pfaffinger ◽  
Sonja Schmucker ◽  
Ulrike Weiler ◽  
Volker Stefanski
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Plasma Cortisol ◽  
Immune Cell ◽  
Cytotoxic T Cells ◽  
Social Rank ◽  
Γδ T Cells ◽  
Detailed Knowledge ◽  
Immune Functions

During pregnancy, the maternal immune system is characterized by a shift from adaptive to innate immune functions. Besides, the immune system can be influenced by social rank. Detailed knowledge of pregnancy-associated immune changes and of the interplay of rank-associated and gestation-induced immunomodulations is still fragmentary in sows. This study investigates both the numbers of various blood leukocyte subpopulations during pregnancy and the influence of social rank position on progressing pregnancy-associated alterations in group-housed sows. Sows were classified as low (LR), middle (MR), or high-ranking (HR). Five blood samples were collected from each of the 35 sows throughout pregnancy to evaluate the distribution of blood lymphocyte subpopulations and plasma cortisol concentrations. The numbers of T, natural killer (NK), and B cells, cytotoxic T cells (CTL), and CD8+ γδ- T cells decreased during the last trimester of pregnancy, while neutrophils and plasma cortisol concentration increased before parturition. Social rank revealed different effects on B cells and monocytes with MR sows showing higher numbers than LR sows. Plasma cortisol concentrations also tended to be higher in MR sows as compared to LR sows. In conclusion, sows show pregnancy-associated alterations in the immune system, which are influenced by social rank, as middle-ranking sows in particular display signs of stress-induced immunomodulations.

scholarly journals The Influence of Aging and Sex Hormones on Expression of Growth Hormone-Releasing Hormone in the Human Immune System1

2001 ◽  
Vol 86 (7) ◽  
pp. 3157-3161
Author(s):  
O. Khorram ◽  
M. Garthwaite ◽  
T. Golos
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Mrna Expression ◽  
Postmenopausal Women ◽  
Cell Line ◽  
Immune Cell ◽  
Hormone Replacement ◽  
Men And Women

GHRH is a neuropeptide that has also been localized to the immune system. The physiological function of GHRH in the immune system has not been elucidated. This study was conducted to determine whether immune GHRH expression is altered in certain pathological states, such as immune cell tumors, and whether gender, aging, and alterations in the sex steroid milieu influence the expression of this peptide in immune cells. Using double color flow cytometry, GHRH protein was found to be expressed in less than 2% of peripheral blood mononuclear cells (PBMC). Monocytes and B and T cells all expressed GHRH protein, although a greater percentage of T cells compared with B cells and monocytes expressed GHRH (5- to 7-fold). Semiquantitative RT-PCR was used to quantify GHRH messenger ribonucleic acid (mRNA) in PBMC and several immune cell-derived tumors. PBMC and granulocytes expressed low levels of GHRH mRNA with relatively higher levels of expression in monocytes. The tumor cell lines CEMX 174 (B/T cells), HUT 78 (T cells), WIL2-N (B cells), U937 (monocytes/macrophages), and JM 1 (pre-B cell lymphoma) all showed greater expression of GHRH mRNA relative to PBMC. However, two cell lines, CCRF-SB, a B lymphoblastoid cell line, and HL-60, a promyelocytic cell line, expressed GHRH mRNA at similar levels as PBMC. A significant decrease in the percentage of lymphocytes (CD45+ cells) expressing GHRH protein was found in age-advanced men and women compared with young men and women. This decline was noted in B cells (CD20+) and monocytes (CD14+), but not in T cells (CD3+). GHRH mRNA expression in PBMC derived from postmenopausal women was lower than that from premenopausal women. However, no differences in PBMC GHRH mRNA expression were found in young and old men. Although in older men there were fewer peripheral lymphocytes that express GHRH protein, these cells secreted significantly more GHRH in vitro than cells from postmenopausal women with no hormone replacement therapy (HRT), but similar levels as cells from women receiving HRT. PBMC from women receiving HRT secreted more GHRH in vitro than cells from women receiving no hormone replacement. This study demonstrates that the expression of immune GHRH is dynamic, and therefore likely to be regulated. Increased expression of GHRH in certain immune tumors suggests that GHRH may be mitogenic under certain conditions and therefore play a role in the pathogenesis of select immune cell tumors. Collectively, these results suggest a role for GHRH as a local immune modulator and in the pathophysiology of immunosenescence and immune cell tumors.

scholarly journals Immunomodulatory activities of non-commercialized leafy vegetables in KwaZulu-Natal, South Africa

2012 ◽  
Author(s):  
◽  
Berushka Padayachee
Keyword(s):  
T Cells ◽  
B Cells ◽  
Cytotoxic T Cells ◽  
Leafy Vegetables ◽  
Aqueous Extracts ◽  
Immune Functions ◽  
Bidens Pilosa ◽  
Methanolic Extracts ◽  
Ifn Γ ◽  
Asystasia Gangetica

Immunomodulation using plants is of primary interest in scientific communities because it provides an alternative to conventional chemotherapy for a wide range of diseases. It is based on the ability of the plants to effectively modulate immune functions, thus being able to promote positive health and maintain the body’s resistance to infection. This research is aimed to evaluate the immunomodulatory potential of fourteen traditional leafy vegetables from Kwa-Zulu Natal, South Africa on human peripheral blood mononuclear cells (PBMC). In this study the methanolic and aqueous extracts were screened for lymphocyte proliferation using the MTT assay. The cytokine response was evaluated by measuring the secretion of interleukin 10 (IL-10) and interferon-gamma (IFN-γ) using the ELISA assay. The subpopulation of T cells viz., CD4+, CD8+, NK and B cells were measured by flow cytometry. Most of the methanolic extracts stimulated PBMC’s whilst a few suppressed lymphocyte proliferation. Most of the aqueous extracts were inactive. The methanolic extracts of Amaranthus hybridus and Centella asiatica stimulated PBMC’s and showed an increase in IFN-γ secretion and the CD8+ cytotoxic T cells and B cells. Thus, they induced the Tc-1 immune response and stimulated cell mediated immunity. The methanolic extracts of Asystasia gangetica, Bidens pilosa, Emex australis, Justicia flava Momordica balsamina, Oxygonum sinuatum, Senna occidentalis and Sonchus oleraceous and the aqueous extracts of Amaranthus spinosus and Asystasia gangetica, Ceratotheca triloba, Oxygonum sinuatum, Physalis viscosa and Sonchus oleaceous stimulated PBMC’s and showed an increase in IL-10 secretion and the CD8+ cytotoxic T cells and B cells. Thus, they induced the Tc-2 immune response and stimulated humoral immunity. Also, the methanolic extracts of Amaranthus spinosus and Ceratotheca triloba and the aqueous extracts of Bidens pilosa and Justicia flava increased both IL-10 and IFN-γ secretion and the CD8+ vii cytotoxic T cells indicating the stimulation of both the Tc1 and Tc2 cytokine profiles. The elevated secretion of IFN-γ and IL-10 caused by the extracts can be attributed to the CD8+ cytotoxic T cells and B cells. The findings of this study show that leafy vegetables hold promise as immunomodulatory candidates. They may enhance cell-mediated immune functions by a pro-inflammatory response whilst some can promote humoral immune functions by means of an anti-inflammatory response. Further investigation should be considered on the effect of the extracts on other immune parameters.

scholarly journals Single-Cell Mass Cytometry on Peripheral Blood Identifies Immune Cell Subsets Associated with Primary Biliary Cholangitis

2020 ◽  
Author(s):  
Jin Sung Jang ◽  
Brian Juran ◽  
Kevin Y. Cunningham ◽  
Vinod K. Gupta ◽  
YoungMin Son ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Single Cell ◽  
Peripheral Blood ◽  
Immune Cell ◽  
Memory B Cells ◽  
Primary Biliary Cholangitis ◽  
Mass Cytometry ◽  
Peripheral Immune System

AbstractThe relationship between Primary Biliary Cholangitis (PBC), a chronic cholestatic autoimmune liver disease, and the peripheral immune system remains to be fully understood. Herein, we performed the first mass cytometry (CyTOF)-based, immunophenotyping analysis of the peripheral immune system in PBC at single-cell resolution. CyTOF was performed on peripheral blood mononuclear cells (PBMCs) from PBC patients (n=33) and age-/sex-matched healthy controls (n=33) to obtain immune cell abundance and marker expression profiles. Hiearchical clustering methods were applied to identify immune cell types and subsets significantly associated with PBC. Subsets of gamma-delta T cells (CD3+TCRgd+), CD8+ T cells (CD3+CD8+CD161+PD1+), and memory B cells (CD3-CD19+CD20+CD24+CD27+) were found to have lower abundance in PBC than in control. In contrast, higher abundance of subsets of monocytes and naïve B cells were observed in PBC compared to control. Furthermore, several naïve B cell (CD3-CD19+CD20+CD24-CD27-) subsets were significantly higher in PBC patients with cirrhosis (indicative of late-stage disease) than in those without cirrhosis. Alternatively, subsets of CD8+CD161+ T cells and memory B cells were lower in abundance in cirrhotic relative to non-cirrhotic PBC patients. Future immunophenotyping investigations could lead to better understanding of PBC pathogenesis and progression, and also to the discovery of novel biomarkers and treatment strategies.

scholarly journals Regulation of Immune Functions by Non-Neuronal Acetylcholine (ACh) via Muscarinic and Nicotinic ACh Receptors

2021 ◽  
Vol 22 (13) ◽  
pp. 6818
Author(s):  
Masato Mashimo ◽  
Yasuhiro Moriwaki ◽  
Hidemi Misawa ◽  
Koichiro Kawashima ◽  
Takeshi Fujii
Keyword(s):  
T Cells ◽  
B Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Immune Functions ◽  
Cell Functions ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Cellular And Humoral Immunity ◽  
Ach Receptors

Acetylcholine (ACh) is the classical neurotransmitter in the cholinergic nervous system. However, ACh is now known to regulate various immune cell functions. In fact, T cells, B cells, and macrophages all express components of the cholinergic system, including ACh, muscarinic, and nicotinic ACh receptors (mAChRs and nAChRs), choline acetyltransferase, acetylcholinesterase, and choline transporters. In this review, we will discuss the actions of ACh in the immune system. We will first briefly describe the mechanisms by which ACh is stored in and released from immune cells. We will then address Ca2+ signaling pathways activated via mAChRs and nAChRs on T cells and B cells, highlighting the importance of ACh for the function of T cells, B cells, and macrophages, as well as its impact on innate and acquired (cellular and humoral) immunity. Lastly, we will discuss the effects of two peptide ligands, secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related peptide-1 (SLURP-1) and hippocampal cholinergic neurostimulating peptide (HCNP), on cholinergic activity in T cells. Overall, we stress the fact that ACh does not function only as a neurotransmitter; it impacts immunity by exerting diverse effects on immune cells via mAChRs and nAChRs.

scholarly journals The Aging of γδ T Cells

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1181 ◽  
Author(s):  
Weili Xu ◽  
Zandrea Wan Xuan Lau ◽  
Tamas Fulop ◽  
Anis Larbi
Keyword(s):  
T Cells ◽  
Immune System ◽  
Immune Cell ◽  
Γδ T Cells ◽  
Cell Types ◽  
Developed Countries ◽  
Common Denominator ◽  
Age Related ◽  
The Relationship ◽  
Diverse Interactions

In the coming decades, many developed countries in the world are expecting the “greying” of their populations. This phenomenon poses unprecedented challenges to healthcare systems. Aging is one of the most important risk factors for infections and a myriad of diseases such as cancer, cardiovascular and neurodegenerative diseases. A common denominator that is implicated in these diseases is the immune system. The immune system consists of the innate and adaptive arms that complement each other to provide the host with a holistic defense system. While the diverse interactions between multiple arms of the immune system are necessary for its function, this complexity is amplified in the aging immune system as each immune cell type is affected differently—resulting in a conundrum that is especially difficult to target. Furthermore, certain cell types, such as γδ T cells, do not fit categorically into the arms of innate or adaptive immunity. In this review, we will first introduce the human γδ T cell family and its ligands before discussing parallels in mice. By covering the ontogeny and homeostasis of γδ T cells during their lifespan, we will better capture their evolution and responses to age-related stressors. Finally, we will identify knowledge gaps within these topics that can advance our understanding of the relationship between γδ T cells and aging, as well as age-related diseases such as cancer.

Axioms of mathe- matical immunology

2001 ◽  
Vol 38 (1-4) ◽  
pp. 13-43 ◽  
Author(s):  
T. Szabados ◽  
L. Varga ◽  
T. Bakács ◽  
Gábor Tusnády
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Free Energy ◽  
Immune System ◽  
B Cells ◽  
Positive Selection ◽  
Immune Cell ◽  
Host Cells ◽  
Energy Minimum ◽  
Free Energy Minimum

Current wisdom describes the immune system as a defense against microbial pathogens. It is claimed that the virgin immune system has a capacity to produce antibodies against the entire antigenic universe. We assume, by contrast, that the responding capacity of the immune system is limited. Thus it cannot stand in readiness to deal with a practi- cally endless diversity and abundance of microbes. Axioms and theorems are suggested for a mathematician audience delineating how the immune system could use its limited resources economically. It is suggested that the task of the immune system is twofold: (i) It sustains homeostasis to preserve the genome by constant surveillance of the intracellular antigenic milieu. This is achieved by standardization of the T cell repertoire through a positive selection. The driving force of positive selection is immune cell survival. T cells must constantly seek contact with complementary MHC structures to survive. Such contact is based on molecular complementarity between immune cell receptors and MHC/self-peptide complexes. At the highest level of complementarity a local free energy minimum is achieved, thus a homeostatic system is created. Homeostatic interactions happen at intermediate afinity and are reversible. Alteration in the presented peptides typically decreases complementarity. That pushes the system away from the free energy minimum, which activates T cells. Complementarity is restored when cytotoxic T cells destroy altered (mutated/infected) host cells. (ii) B cells carry out an immune response to foreign proteins what requires a change in the genome. B cells raised under the antigenic in uence of the normal intestinal micro o- ra, self-proteins and alimentary antigens must go through a hypermutation process to be able to produce specific antibodies. It has a certain probability that hypermutation will successfully change the genome in some clones to switch from low afinity IgM antibody production to high afinity IgG production. Interactions (typically antibody antigen reac- tions) in an immune response happen at high afinity and are irreversible. High afinity clones will be selected, stimulated and enriched by the invading microbes. A complete account of the course of an infectious disease must also include a descrip- tion of the ecology of the immune response. It is therefore suggested that during prolonged interaction between host and infectious organism, carried on across many generations, the adaptive antibody population may facilitate the evolution of the natural antibody reper- toire, in accordance with the Baldwin effect in the evolution of instinct (see Appendix 6).

scholarly journals Recovery of the immune system after exercise

2017 ◽  
Vol 122 (5) ◽  
pp. 1077-1087 ◽  
Author(s):  
Jonathan M. Peake ◽  
Oliver Neubauer ◽  
Neil P. Walsh ◽  
Richard J. Simpson
Keyword(s):  
T Cells ◽  
Immune System ◽  
Cell Function ◽  
Immune Cell ◽  
Physiological Stress ◽  
Current Knowledge ◽  
Ex Vivo ◽  
Γδ T Cells ◽  
Peripheral Tissues ◽  
Recovery Sleep

The notion that prolonged, intense exercise causes an “open window” of immunodepression during recovery after exercise is well accepted. Repeated exercise bouts or intensified training without sufficient recovery may increase the risk of illness. However, except for salivary IgA, clear and consistent markers of this immunodepression remain elusive. Exercise increases circulating neutrophil and monocyte counts and reduces circulating lymphocyte count during recovery. This lymphopenia results from preferential egress of lymphocyte subtypes with potent effector functions [e.g., natural killer (NK) cells, γδ T cells, and CD8+ T cells]. These lymphocytes most likely translocate to peripheral sites of potential antigen encounter (e.g., lungs and gut). This redeployment of effector lymphocytes is an integral part of the physiological stress response to exercise. Current knowledge about changes in immune function during recovery from exercise is derived from assessment at the cell population level of isolated cells ex vivo or in blood. This assessment can be biased by large changes in the distribution of immune cells between blood and peripheral tissues during and after exercise. Some evidence suggests that reduced immune cell function in vitro may coincide with changes in vivo and rates of illness after exercise, but more work is required to substantiate this notion. Among the various nutritional strategies and physical therapies that athletes use to recover from exercise, carbohydrate supplementation is the most effective for minimizing immune disturbances during exercise recovery. Sleep is an important aspect of recovery, but more research is needed to determine how sleep disruption influences the immune system of athletes.

scholarly journals Metabolic Control of Autoimmunity and Tissue Inflammation in Rheumatoid Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jingtao Qiu ◽  
Bowen Wu ◽  
Stuart B. Goodman ◽  
Gerald J. Berry ◽  
Jorg J. Goronzy ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
B Cells ◽  
Immune Cell ◽  
Phase 1 ◽  
Disease Process ◽  
Terminal Phase ◽  
Immune Functions ◽  
Biosynthetic Activity ◽  
Tissue Inflammation

Like other autoimmune diseases, rheumatoid arthritis (RA) develops in distinct stages, with each phase of disease linked to immune cell dysfunction. HLA class II genes confer the strongest genetic risk to develop RA. They encode for molecules essential in the activation and differentiation of T cells, placing T cells upstream in the immunopathology. In Phase 1 of the RA disease process, T cells lose a fundamental function, their ability to be self-tolerant, and provide help for autoantibody-producing B cells. Phase 2 begins many years later, when mis-differentiated T cells gain tissue-invasive effector functions, enter the joint, promote non-resolving inflammation, and give rise to clinically relevant arthritis. In Phase 3 of the RA disease process, abnormal innate immune functions are added to adaptive autoimmunity, converting synovial inflammation into a tissue-destructive process that erodes cartilage and bone. Emerging data have implicated metabolic mis-regulation as a fundamental pathogenic pathway in all phases of RA. Early in their life cycle, RA T cells fail to repair mitochondrial DNA, resulting in a malfunctioning metabolic machinery. Mitochondrial insufficiency is aggravated by the mis-trafficking of the energy sensor AMPK away from the lysosomal surface. The metabolic signature of RA T cells is characterized by the shunting of glucose toward the pentose phosphate pathway and toward biosynthetic activity. During the intermediate and terminal phase of RA-imposed tissue inflammation, tissue-residing macrophages, T cells, B cells and stromal cells are chronically activated and under high metabolic stress, creating a microenvironment poor in oxygen and glucose, but rich in metabolic intermediates, such as lactate. By sensing tissue lactate, synovial T cells lose their mobility and are trapped in the tissue niche. The linkage of defective DNA repair, misbalanced metabolic pathways, autoimmunity, and tissue inflammation in RA encourages metabolic interference as a novel treatment strategy during both the early stages of tolerance breakdown and the late stages of tissue inflammation. Defining and targeting metabolic abnormalities provides a new paradigm to treat, or even prevent, the cellular defects underlying autoimmune disease.

747 Evaluation of immune microenvironment of primary lung cancer and synchronous liver metastasis with multispectral imaging system

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A795-A795
Author(s):  
Hyeonbin Cho ◽  
Jae-Hwan Kim ◽  
Ji-Hyun Kim
Keyword(s):  
T Cells ◽  
Liver Metastasis ◽  
Multispectral Imaging ◽  
Immune Cell ◽  
Imaging System ◽  
Cytotoxic T Cells ◽  
Primary Lung Cancer ◽  
Helper T Cells ◽  
Synchronous Liver Metastasis ◽  
Immune Microenvironment

BackgroundCancer immunotherapy (CIT) has substantially improved the survival of cancer patients. However, according to recent studies, liver metastasis was reported to predict worse outcomes for CIT. The main objective of the study is to evaluate the differences in the immune microenvironment (IME) between the primary lung cancer (PL) and synchronous liver metastasis (LM) using a multispectral imaging system.MethodsSix immune markers (CD4, CD8, CTLA-4, granzyme B (GZB), Foxp3 and PD-L1) were analyzed using a multiplex IHC system and inForm program (Akoya) on paired lung-liver samples of 10 patients. Cells were categorized into tumor nest and stroma, and cell counts per unit area were measured for comparison.ResultsThe number of tumor-infiltrating cytotoxic T cells (TIL) in PL (262.5 cells/mm2) was higher than that of LM (113.3 cells/mm2). Additionally, the ratio between the number of TIL and non-TIL was greater in PL (0.31) compared to that of LM (0.26). A similar trend appeared for Helper T cells and regulatory T cells (Treg), as PL consisted of higher numbers of T cells (791.8 Helper T cells/mm2, 195.7 Treg/mm2) than LM (626.3 Helper T cells/mm2, 121.3 Treg/mm2). However, cytotoxic T cells exhibiting GZB+ and CTLA-4- were fewer in PL (140.2 cells/mm2) than in LM (203.3 cells/mm2), and the ratio is 0.69. The mean number of GZB+ TIL in PL (32.5 cells/mm2) was lower than in LM (35.3 cells/mm2), and their proportions among total TIL counts were 0.12 and 0.31, respectively. In PL, GZB+: GZB- ratio is 0.16 while the ratio is 1.91 for LM. A fewer number of TILs exhibiting GZB suggests that PL has lower efficiency in immune response than LM. Another crucial checkpoint receptor that inhibits immune response, CTLA-4, was more prevalent in PL, with CTLA-4+: CTLA-4- ratio in Treg being 0.36 in PL, compared to 0.11 in LM. The tumor proportion score (TPS) of PD-L1 was higher in PL than LM (40.0 vs. 6.6).ConclusionsIn our study, we showed the differences in the numbers of TIL or regulatory T cells and expressions of immune checkpoint receptors (PD-L1, CTLA-4), which significantly influence outcomes for CIT. The study is ongoing to confirm different IME between the PL and LM groups in a larger tumor cohort.ReferencesPeng, Jianhong, et al., Immune Cell Infiltration in the Microenvironment of Liver Oligometastasis from Colorectal Cancer: Intratumoural CD8/CD3 Ratio Is a Valuable Prognostic Index for Patients Undergoing Liver Metastasectomy. Cancers 2019 Dec; 11(12): 1922. https://doi.org/10.3390/cancers11121922Tumeh, Paul C., et al., Liver Metastasis and treatment outcome with Anti-PD-1 monoclonal antibody in patients with melanoma and NSCLC. Cancer Immunol Res 2017 May; 5(5): 417–424. doi: 10.1158/2326-6066.CIR-16-0325Parra, E.R., Immune Cell Profiling in Cancer Using Multiplex Immunofluorescence and Digital Analysis Approaches; Streckfus, C.F., Ed.; IntechOpen: London, UK, 2018; pp. 1–13. doi: 10.5772/intechopen.80380Ribas, A., Hu-Lieskovan, S., What does PD-L1 positive or negative mean?. The Journal of Experimental Medicine 2016;213(13):2835–2840. https://doi.org/10.1084/jem.20161462

scholarly journals T Cells Limit Accumulation of Aggregate Pathology Following Intrastriatal Injection of α-Synuclein Fibrils

2021 ◽  
pp. 1-19
Author(s):  
Sonia George ◽  
Trevor Tyson ◽  
Nolwen L. Rey ◽  
Rachael Sheridan ◽  
Wouter Peelaerts ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Substantia Nigra ◽  
Adaptive Immune System ◽  
Proteinase K ◽  
T And B Cells ◽  
Adaptive Immune ◽  
Immunocompromised Mice ◽  
The Impact

Background: α-Synuclein (α-syn) is the predominant protein in Lewy-body inclusions, which are pathological hallmarks of α- synucleinopathies, such as Parkinson’s disease (PD) and multiple system atrophy (MSA). Other hallmarks include activation of microglia, elevation of pro-inflammatory cytokines, as well as the activation of T and B cells. These immune changes point towards a dysregulation of both the innate and the adaptive immune system. T cells have been shown to recognize epitopes derived from α-syn and altered populations of T cells have been found in PD and MSA patients, providing evidence that these cells can be key to the pathogenesis of the disease. Objective To study the role of the adaptive immune system with respect to α-syn pathology. Methods: We injected human α-syn preformed fibrils (PFFs) into the striatum of immunocompromised mice (NSG) and assessed accumulation of phosphorylated α-syn pathology, proteinase K-resistant α-syn pathology and microgliosis in the striatum, substantia nigra and frontal cortex. We also assessed the impact of adoptive transfer of naïve T and B cells into PFF-injected immunocompromised mice. Results: Compared to wildtype mice, NSG mice had an 8-fold increase in phosphorylated α-syn pathology in the substantia nigra. Reconstituting the T cell population decreased the accumulation of phosphorylated α-syn pathology and resulted in persistent microgliosis in the striatum when compared to non-transplanted mice. Conclusion: Our work provides evidence that T cells play a role in the pathogenesis of experimental α-synucleinopathy.

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