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Article: Errors in Transactions T. S. M. A.

Burt, W J

Daniel's Texas medical journal

2023 Volume 1, Issue 4, Page(s) 186–187

Language	English
Publishing date	2023-03-23
Publishing country	United States
Document type	Journal Article
ISSN	0892-8487
ISSN	0892-8487
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Distribution modeling quantifies collective T

Burt, Philipp / Thurley, Kevin

Science advances

2023 Volume 9, Issue 37, Page(s) eadg7668

Abstract: ... driven mathematical model for T helper 1 versus T follicular helper cell-fate decision dynamics in acute ...

Abstract	Immune responses are tightly regulated by a diverse set of interacting immune cell populations. Alongside decision-making processes such as differentiation into specific effector cell types, immune cells initiate proliferation at the beginning of an inflammation, forming two layers of complexity. Here, we developed a general mathematical framework for the data-driven analysis of collective immune cell dynamics. We identified qualitative and quantitative properties of generic network motifs, and we specified differentiation dynamics by analysis of kinetic transcriptome data. Furthermore, we derived a specific, data-driven mathematical model for T helper 1 versus T follicular helper cell-fate decision dynamics in acute and chronic lymphocytic choriomeningitis virus infections in mice. The model recapitulates important dynamical properties without model fitting and solely by using measured response-time distributions. Model simulations predict different windows of opportunity for perturbation in acute and chronic infection scenarios, with potential implications for optimization of targeted immunotherapy.
MeSH term(s)	Animals ; Mice ; Inflammation ; Cell Differentiation ; Immunotherapy ; Kinetics ; Reaction Time
Language	English
Publishing date	2023-09-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.adg7668
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Article: Letter from Dr. Burt, Sec. T. S. M. A.

Burt, W J

Daniel's Texas medical journal

2023 Volume 1, Issue 10, Page(s) 462–463

Language	English
Publishing date	2023-03-23
Publishing country	United States
Document type	Journal Article
ISSN	0892-8487
ISSN	0892-8487
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Article ; Online: Dissecting the dynamic transcriptional landscape of early T helper cell differentiation into Th1, Th2, and Th1/2 hybrid cells.

Burt, Philipp / Peine, Michael / Peine, Caroline / Borek, Zuzanna / Serve, Sebastian / Floßdorf, Michael / Hegazy, Ahmed N / Höfer, Thomas / Löhning, Max / Thurley, Kevin

Frontiers in immunology

2022 Volume 13, Page(s) 928018

Abstract: Selective differentiation of CD4+ T helper (Th) cells into specialized subsets such as Th1 and Th2 ...

Abstract	Selective differentiation of CD4+ T helper (Th) cells into specialized subsets such as Th1 and Th2 cells is a key element of the adaptive immune system driving appropriate immune responses. Besides those canonical Th-cell lineages, hybrid phenotypes such as Th1/2 cells arise
MeSH term(s)	Cell Differentiation/genetics ; Hybrid Cells ; Lymphocyte Activation ; Th1 Cells ; Th2 Cells
Language	English
Publishing date	2022-08-16
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.928018
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Article ; Online: Identification of T cell responses to the nonstructural glycoproteins in survivors of Crimean-Congo hemorrhagic fever in South Africa.

Maotoana, Makgotso Golda / Burt, Felicity Jane / Goedhals, Dominique

Journal of medical virology

2023 Volume 95, Issue 10, Page(s) e29154

Abstract: ... generate memory T cell responses that are long-lived and this study aimed to further define specific ... viral proteins targeted by the T cell response. The NS ...

Abstract	Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV) is listed as a priority pathogen by the World Health Organization due to the severity of disease, propensity for spread to nonendemic regions, and absence of a vaccine or specific treatment. The immune correlates of protection are not clearly defined and hence the importance of investigating host immune responses in survivors. We have previously shown that survivors generate memory T cell responses that are long-lived and this study aimed to further define specific viral proteins targeted by the T cell response. The NS
MeSH term(s)	Humans ; Hemorrhagic Fever, Crimean ; South Africa ; Leukocytes, Mononuclear ; T-Lymphocytes ; Glycoproteins ; Mucins ; Peptide Library ; Survivors
Chemical Substances	Glycoproteins ; Mucins ; Peptide Library
Language	English
Publishing date	2023-10-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.29154
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Article ; Online: Human fetal T cells: Insights into developmental specialization and mechanisms of lineage transition.

Burt, Trevor D / McCune, Joseph M

Immunological reviews

2023 Volume 315, Issue 1, Page(s) 126–153

Abstract: ... of overlapping lineages. It is now clear, however, that the transition from human fetal-to-adult T cell identity ... which is reflected in their T cell progeny. At a transcriptional level, clusters of genes are up- and down ... the continuous layering of iterative generations of HSPCs and T cells that arise through progressive changes ...

Abstract	The switch from primitive to definitive hematopoiesis occurs early in development through the emergence of a wave of definitive hematopoietic stem cells from intraembryonic sites, supplanting the original primitive population of extraembryonically derived stem cells. When it became clear that unique features of the fetal immune system could not be reproduced by adult stem cells, it was hypothesized that a lineage of definitive fetal hematopoietic stem cells predominates antenatally, ultimately giving way to an emerging wave of adult stem cells and resulting in a "layered" fetal immune system consisting of overlapping lineages. It is now clear, however, that the transition from human fetal-to-adult T cell identity and function does not occur due to a binary switch between distinct fetal and adult lineages. Rather, recent evidence from single cell analysis suggests that during the latter half of fetal development a gradual, progressive transition occurs at the level of hematopoietic stem-progenitor cells (HSPCs) which is reflected in their T cell progeny. At a transcriptional level, clusters of genes are up- and down-regulated with sequenced timing, suggesting that the transition is under the control of master regulatory factors, including epigenetic modifiers. The net effect is still one of "molecular layering," that is, the continuous layering of iterative generations of HSPCs and T cells that arise through progressive changes in gene expression. This review will focus on recent discoveries that elucidate mechanisms of fetal T cell function and the transition from fetal to adult identity. The epigenetic landscape of fetal T cells facilitates their ability to fulfill the dominant fetal mandate of generating tolerance against self, maternal, and environmental antigens by supporting their predisposition to differentiate into CD25
MeSH term(s)	Infant, Newborn ; Humans ; Cell Lineage ; Hematopoietic Stem Cells ; Transcription Factors ; Hematopoiesis/physiology
Chemical Substances	Transcription Factors
Language	English
Publishing date	2023-03-24
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	391796-4
ISSN	1600-065X ; 0105-2896
ISSN (online)	1600-065X
ISSN	0105-2896
DOI	10.1111/imr.13195
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Article: Intratumoral immune triads are required for adoptive T cell therapy-mediated elimination of solid tumors.

Espinosa-Carrasco, Gabriel / Scrivo, Aurora / Zumbo, Paul / Dave, Asim / Betel, Doron / Hellmann, Matthew / Burt, Bryan M / Lee, Hyun-Sung / Schietinger, Andrea

bioRxiv : the preprint server for biology

2023

Abstract: Tumor-reactive CD8 T cells found in cancer patients are frequently dysfunctional, unable to halt ... tumor growth. Adoptive T cell transfer (ACT), the administration of large numbers of ...

Abstract	Tumor-reactive CD8 T cells found in cancer patients are frequently dysfunctional, unable to halt tumor growth. Adoptive T cell transfer (ACT), the administration of large numbers of
Language	English
Publishing date	2023-07-03
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.07.03.547423
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Article ; Online: Homeostatic cytokines reciprocally modulate the emergence of prenatal effector PLZF+CD4+ T cells in humans.

Locher, Veronica / Park, Sara / Bunis, Daniel G / Makredes, Stephanie / Mayer, Margareta / Burt, Trevor D / Fragiadakis, Gabriela K / Halkias, Joanna

JCI insight

2023 Volume 8, Issue 22

Abstract: ... with the emergence of memory CD4+ T cells alongside regulatory T cells by midgestation. We previously identified ... a prenatal specific population of promyelocytic leukemia zinc finger-positive (PLZF+) CD4+ T ... heterogeneity of human prenatal PLZF+CD4+ T cells and identify the compartmentalization of T helper-like (Th ...

Abstract	The development of human prenatal adaptive immunity progresses faster than previously appreciated, with the emergence of memory CD4+ T cells alongside regulatory T cells by midgestation. We previously identified a prenatal specific population of promyelocytic leukemia zinc finger-positive (PLZF+) CD4+ T cells with heightened effector potential that were enriched in the developing intestine and accumulated in the cord blood of infants exposed to prenatal inflammation. However, the signals that drive their tissue distribution and effector maturation are unknown. Here, we define the transcriptional and functional heterogeneity of human prenatal PLZF+CD4+ T cells and identify the compartmentalization of T helper-like (Th-like) effector function across the small intestine (SI) and mesenteric lymph nodes (MLNs). IL-7 was more abundant in the SI relative to the MLNs and drove the preferential expansion of naive PLZF+CD4+ T cells via enhanced STAT5 and MEK/ERK signaling. Exposure to IL-7 was sufficient to induce the acquisition of CD45RO expression and rapid effector function in a subset of PLZF+CD4+ T cells, identifying a human analog of memory phenotype CD4+ T cells. Further, IL-7 modulated the differentiation of Th1- and Th17-like PLZF+CD4+ T cells and thus likely contributes to the anatomic compartmentalization of human prenatal CD4+ T cell effector function.
MeSH term(s)	Female ; Pregnancy ; Humans ; CD4-Positive T-Lymphocytes ; Cytokines/metabolism ; Interleukin-7/metabolism ; Promyelocytic Leukemia Zinc Finger Protein/genetics ; Kruppel-Like Transcription Factors/genetics ; Kruppel-Like Transcription Factors/metabolism
Chemical Substances	Cytokines ; Interleukin-7 ; Promyelocytic Leukemia Zinc Finger Protein ; Kruppel-Like Transcription Factors
Language	English
Publishing date	2023-11-22
Publishing country	United States
Document type	Journal Article
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.164672
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Article ; Online: Incongruity between T cell receptor recognition of breast cancer hotspot mutations ESR1 Y537S and D538G following exogenous peptide loading versus endogenous antigen processing.

Shafer, Paul / Leung, Wingchi K / Woods, Mae / Choi, Jong Min / Rodriguez-Plata, Carlos M / Maknojia, Arushana / Mosquera, Andres / Somes, Lauren K / Joubert, Jarrett / Manliguez, Anthony / Ranjan, Rashi / Burt, Bryan / Lee, Hyun-Sung / Zhang, Bing / Fuqua, Suzanne / Rooney, Cliona / Leen, Ann M / Hoyos, Valentina

Cytotherapy

2024 Volume 26, Issue 3, Page(s) 266–275

Abstract: T cell receptor engineered T cell (TCR T) therapies have shown recent efficacy against certain ... types of solid metastatic cancers. However, to extend TCR T therapies to treat more patients across ... if immunogenic could serve as ideal tumor-specific targets for TCR T therapy to treat this disease. Through IFN-γ ...

Abstract	T cell receptor engineered T cell (TCR T) therapies have shown recent efficacy against certain types of solid metastatic cancers. However, to extend TCR T therapies to treat more patients across additional cancer types, new TCRs recognizing cancer-specific antigen targets are needed. Driver mutations in AKT1, ESR1, PIK3CA, and TP53 are common in patients with metastatic breast cancer (MBC) and if immunogenic could serve as ideal tumor-specific targets for TCR T therapy to treat this disease. Through IFN-γ ELISpot screening of in vitro expanded neopeptide-stimulated T cell lines from healthy donors and MBC patients, we identified reactivity towards 11 of 13 of the mutations. To identify neopeptide-specific TCRs, we then performed single-cell RNA sequencing of one of the T cell lines following neopeptide stimulation. Here, we identified an ESR1 Y537S specific T cell clone, clonotype 16, and an ESR1 Y537S/D538G dual-specific T cell clone, clonotype 21, which were HLA-B40:02 and HLA-C01:02 restricted, respectively. TCR Ts expressing these TCRs recognized and killed target cells pulsed with ESR1 neopeptides with minimal activity against ESR1 WT peptide. However, these TCRs failed to recognize target cells expressing endogenous mutant ESR1. To investigate the basis of this lack of recognition we performed immunopeptidomics analysis of a mutant-overexpressing lymphoblastoid cell line and found that the ESR1 Y537S neopeptide was not endogenously processed, despite binding to HLA-B*40:02 when exogenously pulsed onto the target cell. These results indicate that stimulation of T cells that likely derive from the naïve repertoire with pulsed minimal peptides may lead to the expansion of clones that recognize non-processed peptides, and highlights the importance of using methods that selectively expand T cells with specificity for antigens that are efficiently processed and presented.
MeSH term(s)	Humans ; Female ; Breast Neoplasms/genetics ; Breast Neoplasms/therapy ; Antigen Presentation ; Receptors, Antigen, T-Cell ; Mutation ; Peptides ; HLA-B Antigens/genetics
Chemical Substances	Receptors, Antigen, T-Cell ; Peptides ; HLA-B Antigens
Language	English
Publishing date	2024-01-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2039821-9
ISSN	1477-2566 ; 1465-3249
ISSN (online)	1477-2566
ISSN	1465-3249
DOI	10.1016/j.jcyt.2023.12.002
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Zs.A 5601: Show issues

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Article ; Online: Human fetal T cells: Insights into developmental specialization and mechanisms of lineage transition

Burt, Trevor D. / McCune, Joseph M.

Immunological Reviews. 2023 May, v. 315, no. 1, p. 126-153

2023 , Page(s) 126–153

Abstract: ... of overlapping lineages. It is now clear, however, that the transition from human fetal‐to‐adult T cell identity ... which is reflected in their T cell progeny. At a transcriptional level, clusters of genes are up‐ and down ... the continuous layering of iterative generations of HSPCs and T cells that arise through progressive changes ...

Abstract	The switch from primitive to definitive hematopoiesis occurs early in development through the emergence of a wave of definitive hematopoietic stem cells from intraembryonic sites, supplanting the original primitive population of extraembryonically derived stem cells. When it became clear that unique features of the fetal immune system could not be reproduced by adult stem cells, it was hypothesized that a lineage of definitive fetal hematopoietic stem cells predominates antenatally, ultimately giving way to an emerging wave of adult stem cells and resulting in a “layered” fetal immune system consisting of overlapping lineages. It is now clear, however, that the transition from human fetal‐to‐adult T cell identity and function does not occur due to a binary switch between distinct fetal and adult lineages. Rather, recent evidence from single cell analysis suggests that during the latter half of fetal development a gradual, progressive transition occurs at the level of hematopoietic stem‐progenitor cells (HSPCs) which is reflected in their T cell progeny. At a transcriptional level, clusters of genes are up‐ and down‐regulated with sequenced timing, suggesting that the transition is under the control of master regulatory factors, including epigenetic modifiers. The net effect is still one of “molecular layering,” that is, the continuous layering of iterative generations of HSPCs and T cells that arise through progressive changes in gene expression. This review will focus on recent discoveries that elucidate mechanisms of fetal T cell function and the transition from fetal to adult identity. The epigenetic landscape of fetal T cells facilitates their ability to fulfill the dominant fetal mandate of generating tolerance against self, maternal, and environmental antigens by supporting their predisposition to differentiate into CD25⁺FoxP3⁺ regulatory T cells (TRₑgₛ). We will explore how the coordinated development of two complementary populations of fetal T cells—conventional T cells dominated by TRₑgₛ and tissue‐associated memory effector cells with innate‐like inflammatory potential—is crucial not only for maintaining intrauterine immune quiescence but also for facilitating an immune response that is appropriately tuned for the bombardment of antigen stimulation that happens at birth.
Keywords	T-lymphocytes ; adults ; antigens ; epigenetics ; fetal development ; hematopoiesis ; humans ; immune response ; memory ; progeny ; transcription (genetics)
Language	English
Dates of publication	2023-05
Size	p. 126-153
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	REVIEW
ZDB-ID	391796-4
ISSN	1600-065X ; 0105-2896
ISSN (online)	1600-065X
ISSN	0105-2896
DOI	10.1111/imr.13195
Database	NAL-Catalogue (AGRICOLA)

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