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Article ; Online: The Proteomic Landscape of Resting and Activated CD4+ T Cells Reveal Insights into Cell Differentiation and Function.

Subbannayya, Yashwanth / Haug, Markus / Pinto, Sneha M / Mohanty, Varshasnata / Meås, Hany Zakaria / Flo, Trude Helen / Prasad, T S Keshava / Kandasamy, Richard K

International journal of molecular sciences

2020 Volume 22, Issue 1

Abstract: CD4+ T cells (T helper cells) are cytokine-producing adaptive immune cells that activate or ... regulate the responses of various immune cells. The activation and functional status of CD4+ T cells is ... FTMS-based proteomic profiling of resting and T cell receptor-activated (72 h) primary human CD4+ ...

Abstract	CD4+ T cells (T helper cells) are cytokine-producing adaptive immune cells that activate or regulate the responses of various immune cells. The activation and functional status of CD4+ T cells is important for adequate responses to pathogen infections but has also been associated with auto-immune disorders and survival in several cancers. In the current study, we carried out a label-free high-resolution FTMS-based proteomic profiling of resting and T cell receptor-activated (72 h) primary human CD4+ T cells from peripheral blood of healthy donors as well as SUP-T1 cells. We identified 5237 proteins, of which significant alterations in the levels of 1119 proteins were observed between resting and activated CD4+ T cells. In addition to identifying several known T-cell activation-related processes altered expression of several stimulatory/inhibitory immune checkpoint markers between resting and activated CD4+ T cells were observed. Network analysis further revealed several known and novel regulatory hubs of CD4+ T cell activation, including IFNG, IRF1, FOXP3, AURKA, and RIOK2. Comparison of primary CD4+ T cell proteomic profiles with human lymphoblastic cell lines revealed a substantial overlap, while comparison with mouse CD+ T cell data suggested interspecies proteomic differences. The current dataset will serve as a valuable resource to the scientific community to compare and analyze the CD4+ proteome.
MeSH term(s)	Adaptive Immunity ; Animals ; CD4-Positive T-Lymphocytes/cytology ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; Cell Differentiation/genetics ; Cell Differentiation/immunology ; Cell Line ; Humans ; Immune Checkpoint Proteins/metabolism ; Lymphocyte Activation/genetics ; Lymphocyte Activation/immunology ; Mass Spectrometry ; Mice ; Proteome ; Proteomics/methods ; Signal Transduction
Chemical Substances	Immune Checkpoint Proteins ; Proteome
Language	English
Publishing date	2020-12-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22010275
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Article ; Online: The Proteomic Landscape of Resting and Activated CD4+ T Cells Reveal Insights into Cell Differentiation and Function

Yashwanth Subbannayya / Markus Haug / Sneha M. Pinto / Varshasnata Mohanty / Hany Zakaria Meås / Trude Helen Flo / T. S. Keshava Prasad / Richard K. Kandasamy

International Journal of Molecular Sciences, Vol 22, Iss 275, p

2021 Volume 275

Abstract	CD4+ T cells (T helper cells) are cytokine-producing adaptive immune cells that activate or regulate the responses of various immune cells. The activation and functional status of CD4+ T cells is important for adequate responses to pathogen infections but has also been associated with auto-immune disorders and survival in several cancers. In the current study, we carried out a label-free high-resolution FTMS-based proteomic profiling of resting and T cell receptor-activated (72 h) primary human CD4+ T cells from peripheral blood of healthy donors as well as SUP-T1 cells. We identified 5237 proteins, of which significant alterations in the levels of 1119 proteins were observed between resting and activated CD4+ T cells. In addition to identifying several known T-cell activation-related processes altered expression of several stimulatory/inhibitory immune checkpoint markers between resting and activated CD4+ T cells were observed. Network analysis further revealed several known and novel regulatory hubs of CD4+ T cell activation, including IFNG, IRF1, FOXP3, AURKA, and RIOK2. Comparison of primary CD4+ T cell proteomic profiles with human lymphoblastic cell lines revealed a substantial overlap, while comparison with mouse CD+ T cell data suggested interspecies proteomic differences. The current dataset will serve as a valuable resource to the scientific community to compare and analyze the CD4+ proteome.
Keywords	adaptive immunity ; T-lymphocytes ; CD4+ T helper cells ; mass spectrometry ; proteomics ; label-free quantitation ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	570
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Sensing of HIV-1 by TLR8 activates human T cells and reverses latency.

Meås, Hany Zekaria / Haug, Markus / Beckwith, Marianne Sandvold / Louet, Claire / Ryan, Liv / Hu, Zhenyi / Landskron, Johannes / Nordbø, Svein Arne / Taskén, Kjetil / Yin, Hang / Damås, Jan Kristian / Flo, Trude Helen

Nature communications

2020 Volume 11, Issue 1, Page(s) 147

Abstract: ... CD4+ T cells and potential exposure of the viral ssRNA genome to endosomal Toll-like receptors (TLRs ... in adaptive immune cells is less well understood. Here we show that synthetic ligands of TLR8 boosted T cell ... markers. Adjuvant TLR8 stimulation, but not TLR7 or TLR9, further promoted T helper cell differentiation ...

Abstract	During HIV infection, cell-to-cell transmission results in endosomal uptake of the virus by target CD4+ T cells and potential exposure of the viral ssRNA genome to endosomal Toll-like receptors (TLRs). TLRs are instrumental in activating inflammatory responses in innate immune cells, but their function in adaptive immune cells is less well understood. Here we show that synthetic ligands of TLR8 boosted T cell receptor signaling, resulting in increased cytokine production and upregulation of surface activation markers. Adjuvant TLR8 stimulation, but not TLR7 or TLR9, further promoted T helper cell differentiation towards Th1 and Th17. In addition, we found that endosomal HIV induced cytokine secretion from CD4+ T cells in a TLR8-specific manner. TLR8 engagement also enhanced HIV-1 replication and potentiated the reversal of latency in patient-derived T cells. The adjuvant TLR8 activity in T cells can contribute to viral dissemination in the lymph node and low-grade inflammation in HIV patients. In addition, it can potentially be exploited for therapeutic targeting and vaccine development.
MeSH term(s)	Cell Line ; HIV Infections/immunology ; HIV Infections/transmission ; HIV-1/immunology ; Humans ; Immunity, Innate/immunology ; Signal Transduction/immunology ; Th1 Cells/immunology ; Th17 Cells/immunology ; Toll-Like Receptor 8/immunology ; Toll-Like Receptor 8/metabolism
Chemical Substances	TLR8 protein, human ; Toll-Like Receptor 8
Keywords	covid19
Language	English
Publishing date	2020-01-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-019-13837-4
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Article ; Online: Sensing of HIV-1 by TLR8 activates human T cells and reverses latency

Hany Zekaria Meås / Markus Haug / Marianne Sandvold Beckwith / Claire Louet / Liv Ryan / Zhenyi Hu / Johannes Landskron / Svein Arne Nordbø / Kjetil Taskén / Hang Yin / Jan Kristian Damås / Trude Helen Flo

Nature Communications, Vol 11, Iss 1, Pp 1-

2020 Volume 16

Abstract: Manipulation of Toll-like receptors (TLRs) affects HIV-1 infection and latency reversal. Here, the authors show that HIV-1 is endocytosed and recognized by TLR8 in human primary CD4+T cells and that TLR8 stimulation induces an inflammatory response that ... ...

Abstract	Manipulation of Toll-like receptors (TLRs) affects HIV-1 infection and latency reversal. Here, the authors show that HIV-1 is endocytosed and recognized by TLR8 in human primary CD4+T cells and that TLR8 stimulation induces an inflammatory response that promotes HIV-1 replication and reversal of latency.
Keywords	Science ; Q
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Sensing of HIV-1 by TLR8 activates human T cells and reverses latency

Nature Communications, Vol 11, Iss 1, Pp 1-

2020 Volume 16

Abstract	Manipulation of Toll-like receptors (TLRs) affects HIV-1 infection and latency reversal. Here, the authors show that HIV-1 is endocytosed and recognized by TLR8 in human primary CD4+T cells and that TLR8 stimulation induces an inflammatory response that promotes HIV-1 replication and reversal of latency.
Keywords	Science ; Q
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Humoral and Cellular Immune Responses Induced by Bivalent DNA Vaccines Expressing Fusion Capsid Proteins of Porcine Circovirus Genotypes 2a and 2b.

Meas, Sochanwattey / Chaimongkolnukul, Khuanjit / Narkpuk, Jaraspim / Mekvichitsaeng, Phenjun / Poomputsa, Kanokwan / Wanasen, Nanchaya / Roshorm, Yaowaluck Maprang

Vaccines

2024 Volume 12, Issue 3

Abstract: ... five putative T cell epitopes were identified on Cap2a and Cap2b. Importantly, our DNA vaccines ...

Abstract	Porcine circovirus type 2 (PCV2) is the main causative agent of porcine circovirus-associated disease (PCVAD) that profoundly impacts the swine industry worldwide. While most of the commercial PCV vaccines are developed based on PCV genotype 2a (PCV2a), PCV genotype 2b (PCV2b) has become predominant since 2003. In this study, we developed and evaluated DNA-based bivalent vaccines covering both PCV2a and PCV2b. We generated a new immunogen, PCV2b-2a, by combining consensus sequences of the PCV2a and PCV2b capsid proteins (Cap2a and Cap2b) in a form of fusion protein. We also examined whether modifications of the PCV2b-2a fusion protein with a signal sequence (SS) and granulocyte macrophage-colony stimulating factor (GM-CSF) fusing with interleukine-4 (IL-4) (GI) could further improve the vaccine immunogenicity. An immunogenicity study of BALB/cAJcl mice revealed that the DNA vector pVAX1 co-expressing PCV2b-2a and GI (pVAX1.PCV2b-2a-GI) was most potent at inducing both antibody and cellular immune responses against Cap2a and Cap2b. Interestingly, the vaccines skewed the immune response towards Th1 phenotype (IgG2a > IgG1). By performing ELISA and ELISpot with predicted epitope peptides, the three most immunogenic B cell epitopes and five putative T cell epitopes were identified on Cap2a and Cap2b. Importantly, our DNA vaccines elicited broad immune responses recognizing both genotype-specific and PCV2-conserved epitopes. Sera from mice immunized with the DNAs expressing PCV2b-2a and PCV2b-2a-GI significantly inhibited PCV2a cell entry at serum dilution 1:8. All these results suggest a great potential of our PCV2b-2a-based vaccines, which can be further developed for use in other vaccine platforms to achieve both vaccine efficacy and economical production cost.
Language	English
Publishing date	2024-03-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines12030324
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Article ; Online: Fetal origins of insulin resistance and the metabolic syndrome: a key role for adipose tissue?

Meas, T

Diabetes & metabolism

2009 Volume 36, Issue 1, Page(s) 11–20

Abstract: For several years now, the epidemiological data have shown an inverse relationship between birth-weight and the development in later life of cardiovascular disease and metabolic disorders. The term "small for gestational age" (SGA) describes a neonate ... ...

Abstract	For several years now, the epidemiological data have shown an inverse relationship between birth-weight and the development in later life of cardiovascular disease and metabolic disorders. The term "small for gestational age" (SGA) describes a neonate whose birth-weight is two standard deviations (SD) below the reference mean, corrected for gestational age and gender. SGA is associated with increased risks of developing hypertension, insulin resistance and type2 diabetes. However, the association with an atherogenic lipid profile is less clear. Nevertheless, all of the components of the metabolic syndrome are present. Yet, in spite of the large body of data in the literature, the biological mechanisms underlying this association are still unclear. To explain the association, various hypotheses have been proposed, pointing to the role of a detrimental fetal environment or genetic susceptibility, or interaction between the two, and to the particular dynamic changes in adiposity that occur during catch-up growth. However, not only quantitative, but also qualitative, abnormalities of adipose tissue have been observed, suggesting a critical role of this organ in the development of metabolic complications.
MeSH term(s)	Adipose Tissue/metabolism ; Adult ; Birth Weight ; Cardiovascular Diseases/etiology ; Cardiovascular Diseases/mortality ; Diabetes Mellitus, Type 2/etiology ; Diabetes Mellitus, Type 2/metabolism ; Dyslipidemias/etiology ; Dyslipidemias/metabolism ; Fetus/metabolism ; Finland/epidemiology ; Genetic Predisposition to Disease ; Humans ; Hypertension/etiology ; Hypertension/metabolism ; Infant, Newborn ; Infant, Small for Gestational Age/metabolism ; Insulin/metabolism ; Insulin Resistance ; Insulin Secretion ; Metabolic Syndrome/etiology ; Metabolic Syndrome/genetics ; Metabolic Syndrome/metabolism ; Metabolic Syndrome/physiopathology ; United Kingdom/epidemiology ; Weight Gain
Chemical Substances	Insulin
Language	English
Publishing date	2009-10-07
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	1315751-6
ISSN	1878-1780 ; 1262-3636 ; 0338-1684
ISSN (online)	1878-1780
ISSN	1262-3636 ; 0338-1684
DOI	10.1016/j.diabet.2009.09.001
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Article: Membrane-cytoskeleton interactions during the formation of the immunological synapse and subsequent T-cell activation.

Das, Vincent / Nal, Béatrice / Roumier, Anne / Meas-Yedid, Vannary / Zimmer, Christophe / Olivo-Marin, Jean-Christophe / Roux, Pascal / Ferrier, Pierre / Dautry-Varsat, Alice / Alcover, Andrés

Immunological reviews

2002 Volume 189, Page(s) 123–135

Abstract: Upon antigen recognition, T cells undergo substantial membrane and cytoskeletal rearrangements ... that lead to the formation of the immunological synapse and are necessary for subsequent T-cell activation ... of the cytoskeleton-mediated architecture of the immunological synapse that plays a role in T-cell receptor clustering ...

Abstract	Upon antigen recognition, T cells undergo substantial membrane and cytoskeletal rearrangements that lead to the formation of the immunological synapse and are necessary for subsequent T-cell activation. However, little is known about how membrane and cytoskeletal molecules interact during these processes. Here we discuss the involvement of the membrane-microfilament linker ezrin. We propose that ezrin is a component of the cytoskeleton-mediated architecture of the immunological synapse that plays a role in T-cell receptor clustering, protein kinase C theta translocation and intracellular signaling.
MeSH term(s)	4-Butyrolactone/analogs & derivatives ; 4-Butyrolactone/immunology ; Actins/immunology ; Animals ; Antigen-Presenting Cells/immunology ; CD3 Complex/metabolism ; Cell Polarity ; Cytoskeletal Proteins ; Cytoskeleton/immunology ; Humans ; Image Processing, Computer-Assisted ; Intercellular Junctions/immunology ; Lymphocyte Activation ; Mice ; Models, Immunological ; Phosphoproteins/chemistry ; Phosphoproteins/immunology ; Receptors, Antigen, T-Cell/metabolism ; T-Lymphocytes/immunology
Chemical Substances	Actins ; CD3 Complex ; Cytoskeletal Proteins ; Phosphoproteins ; Receptors, Antigen, T-Cell ; coronin ; ezrin ; 4-Butyrolactone (OL659KIY4X)
Language	English
Publishing date	2002-11-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	391796-4
ISSN	1600-065X ; 0105-2896
ISSN (online)	1600-065X
ISSN	0105-2896
DOI	10.1034/j.1600-065x.2002.18911.x
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Article: Thermodynamic design optimisation of an open air recuperative twin-shaft solar thermal Brayton cycle with combined or exclusive reheating and intercooling

Meas, M.R / T. Bello-Ochende

Energy conversion and management. 2017 Sept. 15, v. 148

2017

Abstract: The present work applies the method of entropy generation minimisation to investigate the effects of reheating and intercooling on the optimal design and maximum net power output of an open recuperative solar thermal Brayton cycle. Three cases are ... ...

Abstract	The present work applies the method of entropy generation minimisation to investigate the effects of reheating and intercooling on the optimal design and maximum net power output of an open recuperative solar thermal Brayton cycle. Three cases are considered. The intercooled cycle demonstrates both the greatest net power output per unit collector area and the highest ratio of total irreversibility to heat input, followed by the combined and reheated cycles, respectively. Temperature differences across the components are identified as the primary cause of entropy generation. The receivers are found to be the primary site of entropy generation in all cases, and entropy generation in the intercoolers found to constitute the smallest proportion of the total entropy production rate. The optimised heat exchanger lengths are shown to lie on the maximum constraints, and the channel cross-sections found to constrict with increasing mass flow rate such that the total plate surface area is increased to promote heat transfer. The receiver and reheater geometric parameters are found to vary such that the absorber tube surface temperatures are kept below the maximum constraint, and the trends in the optimal parameters for receivers and reheaters comprising circular cross-section absorber tubes found to fluctuate considerably.
Keywords	air ; entropy ; heat exchangers ; heat transfer ; mass flow ; surface area ; surface temperature
Language	English
Dates of publication	2017-0915
Size	p. 770-784.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	2000891-0
ISSN	0196-8904
ISSN	0196-8904
DOI	10.1016/j.enconman.2017.06.043
Database	NAL-Catalogue (AGRICOLA)

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Article: Automatic diagnosis and classification of breast surgical samples with dynamic full-field OCT and machine learning.

Scholler, Jules / Mandache, Diana / Mathieu, Marie Christine / Lakhdar, Aïcha Ben / Darche, Marie / Monfort, Tual / Boccara, Claude / Olivo-Marin, Jean-Christophe / Grieve, Kate / Meas-Yedid, Vannary / la Guillaume, Emilie Benoit A / Thouvenin, Olivier

Journal of medical imaging (Bellingham, Wash.)

2023 Volume 10, Issue 3, Page(s) 34504

Abstract: Purpose: The adoption of emerging imaging technologies in the medical community is often hampered when they provide a new unfamiliar contrast that requires experience to be interpreted. Dynamic full-field optical coherence tomography (D-FF-OCT) ... ...

Abstract	Purpose: The adoption of emerging imaging technologies in the medical community is often hampered when they provide a new unfamiliar contrast that requires experience to be interpreted. Dynamic full-field optical coherence tomography (D-FF-OCT) microscopy is such an emerging technique. It provides fast, high-resolution images of excised tissues with a contrast comparable to H&E histology but without any tissue preparation and alteration. Approach: We designed and compared two machine learning approaches to support interpretation of D-FF-OCT images of breast surgical specimens and thus provide tools to facilitate medical adoption. We conducted a pilot study on 51 breast lumpectomy and mastectomy surgical specimens and more than 1000 individual Results: Using our automatic diagnosis algorithms, we obtained an accuracy above 88% at the image level ( Conclusions: Altogether, these results demonstrate the high potential of D-FF-OCT coupled to machine learning to provide a rapid, automatic, and accurate histopathology diagnosis with minimal sample alteration.
Language	English
Publishing date	2023-06-01
Publishing country	United States
Document type	Journal Article
ISSN	2329-4302
ISSN	2329-4302
DOI	10.1117/1.JMI.10.3.034504
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