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Article ; Online: Cutting Edge: First Lung Infection Permanently Enlarges Lymph Nodes and Enhances New T Cell Responses.

Stolley, J Michael / Scott, Milcah C / O'Flanagan, Stephen D / Künzli, Marco / Matson, Courtney A / Weyu, Eyob / Langlois, Ryan A / Vezys, Vaiva / Masopust, David

Journal of immunology (Baltimore, Md. : 1950)

2024

Abstract: Humans experience frequent respiratory infections. Immunology and vaccinology studies in mice are typically performed in naive specific pathogen-free animals responding to their very first respiratory challenge. We found that the first respiratory ... ...

Abstract	Humans experience frequent respiratory infections. Immunology and vaccinology studies in mice are typically performed in naive specific pathogen-free animals responding to their very first respiratory challenge. We found that the first respiratory infection induces lifelong enlargement of the lung-draining mediastinal lymph nodes (medLNs). Furthermore, infection-experienced medLNs supported better naive T cell surveillance and effector responses to new unrelated infections that exhibited more biased accumulation and memory establishment within the lung. Moreover, we observed that weight loss induced by influenza infection was substantially reduced in mice that had recovered from a previous unrelated respiratory viral challenge. These data show that the lack of infectious history and corresponding medLN hypoplasia in specific pathogen-free mice alter their immune response to lung infections. Preclinical vaccination and immunology studies should consider the previous infectious experience of the model organism.
Language	English
Publishing date	2024-04-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2400010
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Article ; Online: Chronic antigen in solid tumors drives a distinct program of T cell residence.

Gavil, Noah V / Scott, Milcah C / Weyu, Eyob / Smith, Olivia C / O'Flanagan, Stephen D / Wijeyesinghe, Sathi / Lotfi-Emran, Sahar / Shiao, Stephen L / Vezys, Vaiva / Masopust, David

Science immunology

2023 Volume 8, Issue 84, Page(s) eadd5976

Abstract: Analyses of healthy tissue reveal signatures that identify resident memory ... ...

Abstract	Analyses of healthy tissue reveal signatures that identify resident memory CD8
MeSH term(s)	Mice ; Animals ; CD8-Positive T-Lymphocytes ; Immunologic Memory ; Neoplasms ; Antigens ; Prognosis ; Tumor Microenvironment
Chemical Substances	Antigens
Language	English
Publishing date	2023-06-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2470-9468
ISSN (online)	2470-9468
DOI	10.1126/sciimmunol.add5976
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Article ; Online: Functional T cells are capable of supernumerary cell division and longevity.

Soerens, Andrew G / Künzli, Marco / Quarnstrom, Clare F / Scott, Milcah C / Swanson, Lee / Locquiao, J J / Ghoneim, Hazem E / Zehn, Dietmar / Youngblood, Benjamin / Vezys, Vaiva / Masopust, David

Nature

2023 Volume 614, Issue 7949, Page(s) 762–766

Abstract: Differentiated somatic mammalian cells putatively exhibit species-specific division limits that impede cancer but may constrain ... ...

Abstract	Differentiated somatic mammalian cells putatively exhibit species-specific division limits that impede cancer but may constrain lifespans
MeSH term(s)	Animals ; Mice ; CD8-Positive T-Lymphocytes/cytology ; CD8-Positive T-Lymphocytes/immunology ; Cell Differentiation ; Cell Division ; Immunologic Memory ; Longevity/immunology ; Neoplasms/immunology ; Neoplasms/pathology ; T-Lymphocytes/cytology ; T-Lymphocytes/immunology ; Cellular Senescence/immunology ; Cellular Senescence/physiology ; Lymphocyte Activation ; Immunization, Secondary ; Vaccination ; Adoptive Transfer ; Time Factors ; Infections/immunology ; Chronic Disease ; Epigenesis, Genetic
Chemical Substances	Pdcd1 protein, mouse
Language	English
Publishing date	2023-01-18
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-022-05626-9
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Article ; Online: Depleting CD103+ resident memory T cells in vivo reveals immunostimulatory functions in oral mucosa.

Stolley, J Michael / Scott, Milcah C / Joag, Vineet / Dale, Alexander J / Johnston, Timothy S / Saavedra, Flavia / Gavil, Noah V / Lotfi-Emran, Sahar / Soerens, Andrew G / Weyu, Eyob / Pierson, Mark J / Herzberg, Mark C / Zhang, Nu / Vezys, Vaiva / Masopust, David

The Journal of experimental medicine

2023 Volume 220, Issue 7

Abstract: The oral mucosa is a frontline for microbial exposure and juxtaposes several unique tissues and mechanical structures. Based on parabiotic surgery of mice receiving systemic viral infections or co-housing with microbially diverse pet shop mice, we report ...

Abstract	The oral mucosa is a frontline for microbial exposure and juxtaposes several unique tissues and mechanical structures. Based on parabiotic surgery of mice receiving systemic viral infections or co-housing with microbially diverse pet shop mice, we report that the oral mucosa harbors CD8+ CD103+ resident memory T cells (TRM), which locally survey tissues without recirculating. Oral antigen re-encounter during the effector phase of immune responses potentiated TRM establishment within tongue, gums, palate, and cheek. Upon reactivation, oral TRM triggered changes in somatosensory and innate immune gene expression. We developed in vivo methods for depleting CD103+ TRM while sparing CD103neg TRM and recirculating cells. This revealed that CD103+ TRM were responsible for inducing local gene expression changes. Oral TRM putatively protected against local viral infection. This study provides methods for generating, assessing, and in vivo depleting oral TRM, documents their distribution throughout the oral mucosa, and provides evidence that TRM confer protection and trigger responses in oral physiology and innate immunity.
MeSH term(s)	Animals ; Mice ; Antigens/metabolism ; CD8-Positive T-Lymphocytes ; Immunologic Memory ; Memory T Cells ; Mouth Mucosa
Chemical Substances	Antigens ; alpha E integrins
Language	English
Publishing date	2023-04-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20221853
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Article ; Online: Novel Lymphocytic Choriomeningitis Virus Strain Sustains Abundant Exhausted Progenitor CD8 T Cells without Systemic Viremia.

Beura, Lalit K / Scott, Milcah C / Pierson, Mark J / Joag, Vineet / Wijeyesinghe, Sathi / Semler, Matthew R / Quarnstrom, Clare F / Busman-Sahay, Kathleen / Estes, Jacob D / Hamilton, Sara E / Vezys, Vaiva / O'Connor, David H / Masopust, David

Journal of immunology (Baltimore, Md. : 1950)

2022 Volume 209, Issue 9, Page(s) 1691–1702

Abstract: Lymphocytic choriomeningitis virus (LCMV) is the prototypic arenavirus and a natural mouse pathogen. LCMV-Armstrong, an acutely resolved strain, and LCMV-clone 13, a mutant that establishes chronic infection, have provided contrasting infection models ... ...

Abstract	Lymphocytic choriomeningitis virus (LCMV) is the prototypic arenavirus and a natural mouse pathogen. LCMV-Armstrong, an acutely resolved strain, and LCMV-clone 13, a mutant that establishes chronic infection, have provided contrasting infection models that continue to inform the fundamental biology of T cell differentiation, regulation of exhaustion, and response to checkpoint blockade. In this study, we report the isolation and characterization of LCMV-Minnesota (LCMV-MN), which was naturally transmitted to laboratory mice upon cohousing with pet shop mice and shares 80-95% amino acid homology with previously characterized LCMV strains. Infection of laboratory mice with purified LCMV-MN resulted in viral persistence that was intermediate between LCMV-Armstrong and -clone 13, with widely disseminated viral replication and viremia that was controlled within 15-30 d, unless CD4 T cells were depleted prior to infection. LCMV-MN-responding CD8
MeSH term(s)	Amino Acids/metabolism ; Animals ; CD8-Positive T-Lymphocytes ; Hepatitis A Virus Cellular Receptor 2/metabolism ; Lymphocytic Choriomeningitis ; Lymphocytic choriomeningitis virus ; Mice ; Mice, Inbred C57BL ; Programmed Cell Death 1 Receptor ; Viremia/metabolism
Chemical Substances	Amino Acids ; Hepatitis A Virus Cellular Receptor 2 ; Programmed Cell Death 1 Receptor
Language	English
Publishing date	2022-09-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2200320
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Article ; Online: Understanding the Osteosarcoma Pathobiology

Jyotika Varshney / Milcah C. Scott / David A. Largaespada / Subbaya Subramanian

Veterinary Sciences, Vol 3, Iss 1, p

A Comparative Oncology Approach

2016 Volume 3

Abstract: Osteosarcoma is an aggressive primary bone tumor in humans and is among the most common cancer afflicting dogs. Despite surgical advancements and intensification of chemo- and targeted therapies, the survival outcome for osteosarcoma patients is, as of ... ...

Abstract	Osteosarcoma is an aggressive primary bone tumor in humans and is among the most common cancer afflicting dogs. Despite surgical advancements and intensification of chemo- and targeted therapies, the survival outcome for osteosarcoma patients is, as of yet, suboptimal. The presence of metastatic disease at diagnosis or its recurrence after initial therapy is a major factor for the poor outcomes. It is thought that most human and canine patients have at least microscopic metastatic lesions at diagnosis. Osteosarcoma in dogs occurs naturally with greater frequency and shares many biological and clinical similarities with osteosarcoma in humans. From a genetic perspective, osteosarcoma in both humans and dogs is characterized by complex karyotypes with highly variable structural and numerical chromosomal aberrations. Similar molecular abnormalities have been observed in human and canine osteosarcoma. For instance, loss of TP53 and RB regulated pathways are common. While there are several oncogenes that are commonly amplified in both humans and dogs, such as MYC and RAS, no commonly activated proto-oncogene has been identified that could form the basis for targeted therapies. It remains possible that recurrent aberrant gene expression changes due to gene amplification or epigenetic alterations could be uncovered and these could be used for developing new, targeted therapies. However, the remarkably high genomic complexity of osteosarcoma has precluded their definitive identification. Several advantageous murine models of osteosarcoma have been generated. These include spontaneous and genetically engineered mouse models, including a model based on forward genetics and transposon mutagenesis allowing new genes and genetic pathways to be implicated in osteosarcoma development. The proposition of this review is that careful comparative genomic studies between human, canine and mouse models of osteosarcoma may help identify commonly affected and targetable pathways for alternative therapies for osteosarcoma patients. ...
Keywords	osteosarcoma ; comparative oncology ; microRNAs ; prognosis ; canine osteosarcoma ; Veterinary medicine ; SF600-1100
Subject code	570
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Understanding the Osteosarcoma Pathobiology: A Comparative Oncology Approach.

Varshney, Jyotika / Scott, Milcah C / Largaespada, David A / Subramanian, Subbaya

Veterinary sciences

2016 Volume 3, Issue 1

Abstract	Osteosarcoma is an aggressive primary bone tumor in humans and is among the most common cancer afflicting dogs. Despite surgical advancements and intensification of chemo- and targeted therapies, the survival outcome for osteosarcoma patients is, as of yet, suboptimal. The presence of metastatic disease at diagnosis or its recurrence after initial therapy is a major factor for the poor outcomes. It is thought that most human and canine patients have at least microscopic metastatic lesions at diagnosis. Osteosarcoma in dogs occurs naturally with greater frequency and shares many biological and clinical similarities with osteosarcoma in humans. From a genetic perspective, osteosarcoma in both humans and dogs is characterized by complex karyotypes with highly variable structural and numerical chromosomal aberrations. Similar molecular abnormalities have been observed in human and canine osteosarcoma. For instance, loss of
Language	English
Publishing date	2016-01-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2768971-2
ISSN	2306-7381 ; 2306-7381
ISSN (online)	2306-7381
ISSN	2306-7381
DOI	10.3390/vetsci3010003
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Article ; Online: Developmental plasticity allows outside-in immune responses by resident memory T cells.

Fonseca, Raissa / Beura, Lalit K / Quarnstrom, Clare F / Ghoneim, Hazem E / Fan, Yiping / Zebley, Caitlin C / Scott, Milcah C / Fares-Frederickson, Nancy J / Wijeyesinghe, Sathi / Thompson, Emily A / Borges da Silva, Henrique / Vezys, Vaiva / Youngblood, Benjamin / Masopust, David

Nature immunology

2020 Volume 21, Issue 4, Page(s) 412–421

Abstract: Central memory T ( ... ...

Abstract	Central memory T (T
MeSH term(s)	Animals ; Cell Differentiation/immunology ; Cell Plasticity/immunology ; Female ; Immunologic Memory/immunology ; Intestinal Mucosa/immunology ; Intestine, Small/immunology ; Mice ; Mice, Inbred C57BL ; T-Lymphocyte Subsets/immunology
Keywords	covid19
Language	English
Publishing date	2020-02-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-020-0607-7
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Article ; Online: Comparative analysis of genome-wide DNA methylation identifies patterns that associate with conserved transcriptional programs in osteosarcoma.

Mills, Lauren J / Scott, Milcah C / Shah, Pankti / Cunanan, Anne R / Deshpande, Archana / Auch, Benjamin / Curtin, Bridget / Beckman, Kenneth B / Spector, Logan G / Sarver, Aaron L / Subramanian, Subbaya / Richmond, Todd A / Modiano, Jaime F

Bone

2020 Volume 158, Page(s) 115716

Abstract: Osteosarcoma is an aggressive tumor of the bone that primarily affects young adults and adolescents. Osteosarcoma is characterized by genomic chaos and heterogeneity. While inactivation of tumor protein p53 (TP53) is nearly universal other high frequency ...

Abstract	Osteosarcoma is an aggressive tumor of the bone that primarily affects young adults and adolescents. Osteosarcoma is characterized by genomic chaos and heterogeneity. While inactivation of tumor protein p53 (TP53) is nearly universal other high frequency mutations or structural variations have not been identified. Despite this genomic heterogeneity, key conserved transcriptional programs associated with survival have been identified across human, canine and induced murine osteosarcoma. The epigenomic landscape, including DNA methylation, plays a key role in establishing transcriptional programs in all cell types. The role of epigenetic dysregulation has been studied in a variety of cancers but has yet to be explored at scale in osteosarcoma. Here we examined genome-wide DNA methylation patterns in 24 human and 44 canine osteosarcoma samples identifying groups of highly correlated DNA methylation marks in human and canine osteosarcoma samples. We also link specific DNA methylation patterns to key transcriptional programs in both human and canine osteosarcoma. Building on previous work, we built a DNA methylation-based measure for the presence and abundance of various immune cell types in osteosarcoma. Finally, we determined that the underlying state of the tumor, and not changes in cell composition, were the main driver of differences in DNA methylation across the human and canine samples. SIGNIFICANCE: Genome wide comparison of DNA methylation patterns in osteosarcoma across two species lays the ground work for the exploration of DNA methylation programs that help establish conserved transcriptional programs in the context of varied mutational landscapes.
MeSH term(s)	Animals ; Bone Neoplasms/genetics ; DNA Methylation/genetics ; Dogs ; Epigenomics ; Genomics ; Mice ; Osteosarcoma/genetics ; Osteosarcoma/pathology
Language	English
Publishing date	2020-10-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	632515-4
ISSN	1873-2763 ; 8756-3282
ISSN (online)	1873-2763
ISSN	8756-3282
DOI	10.1016/j.bone.2020.115716
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Zs.A 1571: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: CD4

Beura, Lalit K / Fares-Frederickson, Nancy J / Steinert, Elizabeth M / Scott, Milcah C / Thompson, Emily A / Fraser, Kathryn A / Schenkel, Jason M / Vezys, Vaiva / Masopust, David

The Journal of experimental medicine

2019 Volume 216, Issue 5, Page(s) 1214–1229

Abstract: This study examines the extent to which memory ... ...

Abstract	This study examines the extent to which memory CD4
MeSH term(s)	Animals ; Arenaviridae Infections/immunology ; Arenaviridae Infections/virology ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cell Movement/immunology ; Chimera/immunology ; Female ; Granzymes/metabolism ; Immunologic Memory/immunology ; Immunologic Surveillance/immunology ; Lymphocytic choriomeningitis virus/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Phenotype ; RNA-Seq ; Transcriptome
Chemical Substances	Granzymes (EC 3.4.21.-) ; Gzmb protein, mouse (EC 3.4.21.-)
Language	English
Publishing date	2019-03-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20181365
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