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Article ; Online: The gene regulatory basis of bystander activation in CD8

Science immunology

2024 Volume 9, Issue 92, Page(s) eadf8776

Abstract: ... ...

Abstract	CD8
MeSH term(s)	Humans ; Adult ; Mice ; Animals ; CD8-Positive T-Lymphocytes ; Immunity, Innate ; Cytokines ; T-Lymphocyte Subsets ; Antigens
Chemical Substances	Cytokines ; Antigens
Language	English
Publishing date	2024-02-23
Publishing country	United States
Document type	Journal Article
ISSN	2470-9468
ISSN (online)	2470-9468
DOI	10.1126/sciimmunol.adf8776
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Article ; Online: Epigenetic scarring of exhausted T cells hinders memory differentiation upon eliminating chronic antigenic stimulation.

Abdel-Hakeem, Mohamed S / Manne, Sasikanth / Beltra, Jean-Christophe / Stelekati, Erietta / Chen, Zeyu / Nzingha, Kito / Ali, Mohammed-Alkhatim / Johnson, John L / Giles, Josephine R / Mathew, Divij / Greenplate, Allison R / Vahedi, Golnaz / Wherry, E John

Nature immunology

2021 Volume 22, Issue 8, Page(s) 1008–1019

Abstract: Exhausted CD8 T cells ( ... ...

Abstract	Exhausted CD8 T cells (T
MeSH term(s)	Animals ; Antigens, Viral/immunology ; CD8-Positive T-Lymphocytes/cytology ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/pathology ; Cell Differentiation/immunology ; Cell Line ; Chlorocebus aethiops ; Cricetinae ; Epigenesis, Genetic/genetics ; Female ; Hepatocyte Nuclear Factor 1-alpha/metabolism ; Immunologic Memory/immunology ; Lymphocytic Choriomeningitis/immunology ; Lymphocytic choriomeningitis virus/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Transcription, Genetic/genetics ; Vero Cells
Chemical Substances	Antigens, Viral ; Hepatocyte Nuclear Factor 1-alpha ; Hnf1a protein, mouse
Language	English
Publishing date	2021-07-26
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/s41590-021-00975-5
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Zs.A 5294: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 42: Show issues

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Article ; Online: Author Correction: Epigenetic scarring of exhausted T cells hinders memory differentiation upon eliminating chronic antigenic stimulation.

Nature immunology

2021 Volume 22, Issue 11, Page(s) 1465

Language	English
Publishing date	2021-09-29
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-021-01057-2
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Zs.A 5294: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 42: Show issues

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Article ; Online: MicroRNA-29a attenuates CD8 T cell exhaustion and induces memory-like CD8 T cells during chronic infection.

Stelekati, Erietta / Cai, Zhangying / Manne, Sasikanth / Chen, Zeyu / Beltra, Jean-Christophe / Buchness, Lance Alec / Leng, Xuebing / Ristin, Svetlana / Nzingha, Kito / Ekshyyan, Viktoriya / Niavi, Christina / Abdel-Hakeem, Mohamed S / Ali, Mohammed-Alkhatim / Drury, Sydney / Lau, Chi Wai / Gao, Zhen / Ban, Yuguang / Zhou, Simon K / Ansel, K Mark /

Kurachi, Makoto / Jordan, Martha S / Villarino, Alejandro V / Ngiow, Shin Foong / Wherry, E John

Proceedings of the National Academy of Sciences of the United States of America

2022 Volume 119, Issue 17, Page(s) e2106083119

Abstract: CD8 T cells mediate protection against intracellular pathogens and tumors. However, persistent antigen during chronic infections or cancer leads to T cell exhaustion, suboptimal functionality, and reduced protective capacity. Despite considerable work ... ...

Abstract	CD8 T cells mediate protection against intracellular pathogens and tumors. However, persistent antigen during chronic infections or cancer leads to T cell exhaustion, suboptimal functionality, and reduced protective capacity. Despite considerable work interrogating the transcriptional regulation of exhausted CD8 T cells (TEX), the posttranscriptional control of TEX remains poorly understood. Here, we interrogated the role of microRNAs (miRs) in CD8 T cells responding to acutely resolved or chronic viral infection and identified miR-29a as a key regulator of TEX. Enforced expression of miR-29a improved CD8 T cell responses during chronic viral infection and antagonized exhaustion. miR-29a inhibited exhaustion-driving transcriptional pathways, including inflammatory and T cell receptor signaling, and regulated ribosomal biogenesis. As a result, miR-29a fostered a memory-like CD8 T cell differentiation state during chronic infection. Thus, we identify miR-29a as a key regulator of TEX and define mechanisms by which miR-29a can divert exhaustion toward a more beneficial memory-like CD8 T cell differentiation state.
MeSH term(s)	CD8-Positive T-Lymphocytes ; Humans ; Immunotherapy/methods ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Neoplasms/metabolism ; Persistent Infection
Chemical Substances	MIRN29a microRNA, human ; MicroRNAs
Language	English
Publishing date	2022-04-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2106083119
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Article ; Online: The Neonatal CD8+ T Cell Repertoire Rapidly Diversifies during Persistent Viral Infection.

Venturi, Vanessa / Nzingha, Kito / Amos, Timothy G / Charles, Wisler C / Dekhtiarenko, Iryna / Cicin-Sain, Luka / Davenport, Miles P / Rudd, Brian D

Journal of immunology (Baltimore, Md. : 1950)

2016 Volume 196, Issue 4, Page(s) 1604–1616

Abstract: CMV is the most common congenital infection in the United States. The major target of congenital CMV is the brain, with clinical manifestations including mental retardation, vision impairment, and sensorineural hearing loss. Previous reports have shown ... ...

Abstract	CMV is the most common congenital infection in the United States. The major target of congenital CMV is the brain, with clinical manifestations including mental retardation, vision impairment, and sensorineural hearing loss. Previous reports have shown that CD8(+) T cells are required to control viral replication and significant numbers of CMV-specific CD8(+) T cells persist in the brain even after the initial infection has been cleared. However, the dynamics of CD8(+) T cells in the brain during latency remain largely undefined. In this report, we used TCR sequencing to track the development and maintenance of neonatal clonotypes in the brain and spleen of mice during chronic infection. Given the discontinuous nature of tissue-resident memory CD8(+) T cells, we hypothesized that neonatal TCR clonotypes would be locked in the brain and persist into adulthood. Surprisingly, we found that the Ag-specific T cell repertoire in neonatal-infected mice diversified during persistent infection in both the brain and spleen, while maintaining substantial similarity between the CD8(+) T cell populations in the brain and spleen in both early and late infection. However, despite the diversification of, and potential interchange between, the spleen and brain Ag-specific T cell repertoires, we observed that germline-encoded TCR clonotypes, characteristic of neonatal infection, persisted in the brain, albeit sometimes in low abundance. These results provide valuable insights into the evolution of CD8(+) T cell repertoires following neonatal CMV infection and thus have important implications for the development of therapeutic strategies to control CMV in early life.
MeSH term(s)	Animals ; Animals, Newborn ; Brain/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cytomegalovirus/immunology ; Cytomegalovirus Infections/immunology ; Genes, T-Cell Receptor ; Immunologic Memory ; Mice, Inbred C57BL ; Receptors, Antigen, T-Cell, alpha-beta/immunology ; Spleen/cytology ; Spleen/immunology
Chemical Substances	Receptors, Antigen, T-Cell, alpha-beta
Language	English
Publishing date	2016-02-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
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.1501867
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Ud II Zs.37: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 28: Show issues

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Article ; Online: Long-Term Persistence of Exhausted CD8 T Cells in Chronic Infection Is Regulated by MicroRNA-155.

Stelekati, Erietta / Chen, Zeyu / Manne, Sasikanth / Kurachi, Makoto / Ali, Mohammed-Alkhatim / Lewy, Keith / Cai, Zhangying / Nzingha, Kito / McLane, Laura M / Hope, Jennifer L / Fike, Adam J / Katsikis, Peter D / Wherry, E John

Cell reports

2018 Volume 23, Issue 7, Page(s) 2142–2156

Abstract: Persistent viral infections and tumors drive development of exhausted T ( ... ...

Abstract	Persistent viral infections and tumors drive development of exhausted T (T
MeSH term(s)	Animals ; CD8-Positive T-Lymphocytes/immunology ; Cell Differentiation ; Cell Proliferation/genetics ; Chronic Disease ; Communicable Diseases/genetics ; Communicable Diseases/immunology ; Communicable Diseases/pathology ; Fos-Related Antigen-2/metabolism ; Gene Expression Regulation ; Lymphocyte Subsets/immunology ; Mice, Inbred C57BL ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Phenotype ; Time Factors ; Transcription Factor AP-1/metabolism ; Transcription, Genetic
Chemical Substances	Fos-Related Antigen-2 ; Fosl2 protein, mouse ; MicroRNAs ; Mirn155 microRNA, mouse ; Transcription Factor AP-1
Language	English
Publishing date	2018-05-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2018.04.038
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Article ; Online: Developmental Origin Governs CD8

Smith, Norah L / Patel, Ravi K / Reynaldi, Arnold / Grenier, Jennifer K / Wang, Jocelyn / Watson, Neva B / Nzingha, Kito / Yee Mon, Kristel J / Peng, Seth A / Grimson, Andrew / Davenport, Miles P / Rudd, Brian D

Cell

2018 Volume 174, Issue 1, Page(s) 117–130.e14

Abstract: Heterogeneity is a hallmark feature of the adaptive immune system in vertebrates. Following infection, naive T cells differentiate into various subsets of effector and memory T cells, which help to eliminate pathogens and maintain long-term immunity. The ...

Abstract	Heterogeneity is a hallmark feature of the adaptive immune system in vertebrates. Following infection, naive T cells differentiate into various subsets of effector and memory T cells, which help to eliminate pathogens and maintain long-term immunity. The current model suggests there is a single lineage of naive T cells that give rise to different populations of effector and memory T cells depending on the type and amounts of stimulation they encounter during infection. Here, we have discovered that multiple sub-populations of cells exist in the naive CD8
MeSH term(s)	Animals ; CD8-Positive T-Lymphocytes/drug effects ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Cell Differentiation ; Cell Line, Tumor ; Chromatin/metabolism ; Cytokines/pharmacology ; Epitopes, T-Lymphocyte/genetics ; Epitopes, T-Lymphocyte/metabolism ; Genes, Developmental ; Immunologic Memory ; Interferon-gamma/metabolism ; Killer Cells, Natural/cytology ; Killer Cells, Natural/metabolism ; Listeria monocytogenes/metabolism ; Listeria monocytogenes/pathogenicity ; Mice ; Mice, Inbred C57BL ; Principal Component Analysis ; T-Lymphocyte Subsets/cytology ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism ; Thymus Gland/transplantation ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcriptome
Chemical Substances	Chromatin ; Cytokines ; Epitopes, T-Lymphocyte ; Transcription Factors ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2018-06-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2018.05.029
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Zs.A 1167: 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)
Zs.MG 58: Show issues

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Article ; Online: Developmental Relationships of Four Exhausted CD8

Immunity

2020 Volume 52, Issue 5, Page(s) 825–841.e8

Abstract: ... ...

Abstract	CD8
MeSH term(s)	Animals ; B7-H1 Antigen/genetics ; B7-H1 Antigen/immunology ; CD8-Positive T-Lymphocytes/cytology ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Cells, Cultured ; Epigenesis, Genetic/genetics ; Epigenesis, Genetic/immunology ; Hepatocyte Nuclear Factor 1-alpha/genetics ; Hepatocyte Nuclear Factor 1-alpha/immunology ; Homeodomain Proteins/genetics ; Homeodomain Proteins/immunology ; Humans ; Immunotherapy/methods ; Mice, Inbred C57BL ; Neoplasms/genetics ; Neoplasms/immunology ; Neoplasms/therapy ; T-Box Domain Proteins/genetics ; T-Box Domain Proteins/immunology ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism ; Transcription, Genetic/genetics ; Transcription, Genetic/immunology
Chemical Substances	B7-H1 Antigen ; Cd274 protein, mouse ; Hepatocyte Nuclear Factor 1-alpha ; Hnf1a protein, mouse ; Homeodomain Proteins ; Rhox8 protein, mouse ; T-Box Domain Proteins ; T-box transcription factor TBX21
Language	English
Publishing date	2020-05-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2020.04.014
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Zs.A 4227: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 69: Show issues

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Article ; Online: Acute neonatal infections 'lock-in' a suboptimal CD8+ T cell repertoire with impaired recall responses.

Rudd, Brian D / Venturi, Vanessa / Smith, Norah L / Nzingha, Kito / Goldberg, Emily L / Li, Gang / Nikolich-Zugich, Janko / Davenport, Miles P

PLoS pathogens

2013 Volume 9, Issue 9, Page(s) e1003572

Abstract: Microbial infection during various stages of human development produces widely different clinical outcomes, yet the links between age-related changes in the immune compartment and functional immunity remain unclear. The ability of the immune system to ... ...

Abstract	Microbial infection during various stages of human development produces widely different clinical outcomes, yet the links between age-related changes in the immune compartment and functional immunity remain unclear. The ability of the immune system to respond to specific antigens and mediate protection in early life is closely correlated with the level of diversification of lymphocyte antigen receptors. We have previously shown that the neonatal primary CD8+ T cell response to replication competent virus is significantly constricted compared to the adult response. In the present study, we have analyzed the subsequent formation of neonatal memory CD8+ T cells and their response to secondary infectious challenge. In particular, we asked whether the less diverse CD8+ T cell clonotypes that are elicited by neonatal vaccination with replication competent virus are 'locked-in' to the adult memory T cell, and thus may compromise the strength of adult immunity. Here we report that neonatal memory CD8+ T cells mediate poor recall responses compared to adults and are comprised of a repertoire of lower avidity T cells. During a later infectious challenge the neonatal memory CD8+ T cells compete poorly with the fully diverse repertoire of naïve adult CD8+ T cells and are outgrown by the adult primary response. This has important implications for the timing of vaccination in early life.
MeSH term(s)	Aging ; Animals ; Animals, Newborn ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/pathology ; DNA, Recombinant/metabolism ; Herpes Simplex/immunology ; Herpes Simplex/prevention & control ; Herpes Simplex/virology ; Herpesvirus 1, Human/genetics ; Herpesvirus 1, Human/immunology ; Herpesvirus 1, Human/metabolism ; Immune System/growth & development ; Immune System/immunology ; Immune System/pathology ; Immunologic Deficiency Syndromes/etiology ; Immunologic Deficiency Syndromes/immunology ; Immunologic Deficiency Syndromes/metabolism ; Immunologic Deficiency Syndromes/pathology ; Immunologic Memory ; Listeria monocytogenes/genetics ; Listeria monocytogenes/immunology ; Listeria monocytogenes/metabolism ; Listeria monocytogenes/pathogenicity ; Listeriosis/immunology ; Listeriosis/microbiology ; Listeriosis/physiopathology ; Listeriosis/prevention & control ; Mice, Inbred Strains ; Models, Immunological ; Receptors, Antigen, T-Cell, alpha-beta/metabolism ; Specific Pathogen-Free Organisms ; Vaccines, Attenuated/adverse effects ; Vaccines, Attenuated/immunology ; Vaccinia/immunology ; Vaccinia/prevention & control ; Vaccinia/virology ; Vaccinia virus/genetics ; Vaccinia virus/immunology ; Vaccinia virus/metabolism ; Virulence
Chemical Substances	DNA, Recombinant ; Receptors, Antigen, T-Cell, alpha-beta ; Vaccines, Attenuated
Language	English
Publishing date	2013-09-12
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7366
ISSN (online)	1553-7374
ISSN	1553-7366
DOI	10.1371/journal.ppat.1003572
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Article ; Online: Inhibitory signaling sustains a distinct early memory CD8

Johnnidis, Jonathan B / Muroyama, Yuki / Ngiow, Shin Foong / Chen, Zeyu / Manne, Sasikanth / Cai, Zhangying / Song, Shufei / Platt, Jesse M / Schenkel, Jason M / Abdel-Hakeem, Mohamed / Beltra, Jean-Christophe / Greenplate, Allison R / Ali, Mohammed-Alkhatim A / Nzingha, Kito / Giles, Josephine R / Harly, Christelle / Attanasio, John / Pauken, Kristen E / Bengsch, Bertram /

Paley, Michael A / Tomov, Vesselin T / Kurachi, Makoto / Vignali, Dario A A / Sharpe, Arlene H / Reiner, Steven L / Bhandoola, Avinash / Johnson, F Bradley / Wherry, E John

Science immunology

2021 Volume 6, Issue 55

Abstract: The developmental origins of memory T cells remain incompletely understood. During the expansion phase of acute viral infection, we identified a distinct subset of virus-specific ... ...

Abstract	The developmental origins of memory T cells remain incompletely understood. During the expansion phase of acute viral infection, we identified a distinct subset of virus-specific CD8
MeSH term(s)	Animals ; Antigens, CD/genetics ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Cell Differentiation/genetics ; Cell Differentiation/immunology ; DNA Damage/immunology ; Disease Models, Animal ; Female ; Hepatocyte Nuclear Factor 1-alpha/metabolism ; Humans ; Immunologic Memory/genetics ; Listeria monocytogenes/immunology ; Listeriosis/immunology ; Listeriosis/microbiology ; Lymphocyte Activation ; Lymphocytic Choriomeningitis/immunology ; Lymphocytic Choriomeningitis/virology ; Lymphocytic choriomeningitis virus/immunology ; Male ; Memory T Cells/immunology ; Memory T Cells/metabolism ; Mice ; Mice, Knockout ; Precursor Cells, T-Lymphoid/immunology ; Precursor Cells, T-Lymphoid/metabolism ; Programmed Cell Death 1 Receptor/genetics
Chemical Substances	Antigens, CD ; CD223 antigen ; Hepatocyte Nuclear Factor 1-alpha ; Hnf1a protein, mouse ; Pdcd1 protein, mouse ; Programmed Cell Death 1 Receptor
Language	English
Publishing date	2021-01-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2470-9468
ISSN (online)	2470-9468
DOI	10.1126/sciimmunol.abe3702
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