LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 44

Search options

  1. Article ; Online: The perception and response of T cells to a changing environment are based on the law of initial value.

    Huseby, Eric S / Teixeiro, Emma

    Science signaling

    2022  Volume 15, Issue 736, Page(s) eabj9842

    Abstract: αβ T cells are critical components of the adaptive immune system and are capable of inducing sterilizing immunity after pathogen infection and eliminating transformed tumor cells. The development and function of T cells are controlled through the T cell ... ...

    Abstract αβ T cells are critical components of the adaptive immune system and are capable of inducing sterilizing immunity after pathogen infection and eliminating transformed tumor cells. The development and function of T cells are controlled through the T cell antigen receptor, which recognizes peptides displayed on major histocompatibility complex (MHC) molecules. Here, we review how T cells generate the ability to recognize self-peptide-bound MHC molecules and use signals derived from these interactions to instruct cellular development, activation thresholds, and functional specialization in the steady state and during immune responses. We argue that the basic tenants of T cell development and function follow Weber-Fetcher's law of just noticeable differences and Wilder's law of initial value. Together, these laws argue that the ability of a system to respond and the quality of that response are scalable to the basal state of that system. Manifestation of these laws in T cells generates clone-specific activation thresholds that are based on perceivable differences between homeostasis and pathogen encounter (self versus nonself discrimination), as well as poised states for subsequent differentiation into specific effector cell lineages.
    MeSH term(s) Cell Differentiation ; Major Histocompatibility Complex ; Perception ; Receptors, Antigen, T-Cell ; T-Lymphocytes
    Chemical Substances Receptors, Antigen, T-Cell
    Language English
    Publishing date 2022-05-31
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2417226-1
    ISSN 1937-9145 ; 1945-0877
    ISSN (online) 1937-9145
    ISSN 1945-0877
    DOI 10.1126/scisignal.abj9842
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article ; Online: How persistent infection overcomes peripheral tolerance mechanisms to cause T cell-mediated autoimmune disease.

    Yin, Rose / Melton, Samuel / Huseby, Eric S / Kardar, Mehran / Chakraborty, Arup K

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

    2024  Volume 121, Issue 11, Page(s) e2318599121

    Abstract: T cells help orchestrate immune responses to pathogens, and their aberrant regulation can trigger autoimmunity. Recent studies highlight that a threshold number of T cells (a quorum) must be activated in a tissue to mount a functional immune response. ... ...

    Abstract T cells help orchestrate immune responses to pathogens, and their aberrant regulation can trigger autoimmunity. Recent studies highlight that a threshold number of T cells (a quorum) must be activated in a tissue to mount a functional immune response. These collective effects allow the T cell repertoire to respond to pathogens while suppressing autoimmunity due to circulating autoreactive T cells. Our computational studies show that increasing numbers of pathogenic peptides targeted by T cells during persistent or severe viral infections increase the probability of activating T cells that are weakly reactive to self-antigens (molecular mimicry). These T cells are easily re-activated by the self-antigens and contribute to exceeding the quorum threshold required to mount autoimmune responses. Rare peptides that activate many T cells are sampled more readily during severe/persistent infections than in acute infections, which amplifies these effects. Experiments in mice to test predictions from these mechanistic insights are suggested.
    MeSH term(s) Animals ; Mice ; Persistent Infection ; Peripheral Tolerance ; T-Lymphocytes ; Autoantigens ; Peptides ; Autoimmune Diseases
    Chemical Substances Autoantigens ; Peptides
    Language English
    Publishing date 2024-03-06
    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.2318599121
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article: The curious case of a cryptic Cryptosporidium and a missing dendritic cell subset

    Lee, Donguk / Huseby, Eric S. / Gowthaman, Uthaman

    Trends in parasitology. 2022 Feb., v. 38, no. 2

    2022  

    Abstract: Animal models for studying immune responses to Cryptosporidium, a parasite that causes gastrointestinal disease, have been a challenge due to the parasite's poor infectivity in mice. Russler-Germain et al. discovered a 'commensal' strain of ... ...

    Abstract Animal models for studying immune responses to Cryptosporidium, a parasite that causes gastrointestinal disease, have been a challenge due to the parasite's poor infectivity in mice. Russler-Germain et al. discovered a 'commensal' strain of Cryptosporidium, capable of stable infection and vertical transmission, that elicits a T helper type 1 (Th1) response to promote intestinal homeostasis.
    Keywords CD4-positive T-lymphocytes ; Cryptosporidium ; dendritic cells ; gastrointestinal diseases ; homeostasis ; intestines ; parasites ; parasitology ; pathogenicity
    Language English
    Dates of publication 2022-02
    Size p. 101-103.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 2036227-4
    ISSN 1471-5007 ; 1471-4922
    ISSN (online) 1471-5007
    ISSN 1471-4922
    DOI 10.1016/j.pt.2021.12.003
    Database NAL-Catalogue (AGRICOLA)

    More links

    Kategorien

  4. Article ; Online: How to Prevent yourself from Seeing Double.

    Stadinski, Brian D / Huseby, Eric S

    Cytometry. Part A : the journal of the International Society for Analytical Cytology

    2020  Volume 97, Issue 11, Page(s) 1102–1104

    MeSH term(s) Biomarkers ; Monocytes ; T-Lymphocytes
    Chemical Substances Biomarkers
    Language English
    Publishing date 2020-06-23
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 2099868-5
    ISSN 1552-4930 ; 0196-4763 ; 1552-4922
    ISSN (online) 1552-4930
    ISSN 0196-4763 ; 1552-4922
    DOI 10.1002/cyto.a.24045
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  5. Article ; Online: Resolving the Instructions for αβ T Cell Development.

    Cleveland, Sarah B / Huseby, Eric S

    Immunity

    2020  Volume 53, Issue 6, Page(s) 1126–1128

    Abstract: In this issue of Immunity, Chopp et. al. use single-cell transcriptomics and epigenomics in mice and human samples to delineate developmental trajectories of αβ T cell subsets and refine the kinetic selection model of ... ...

    Abstract In this issue of Immunity, Chopp et. al. use single-cell transcriptomics and epigenomics in mice and human samples to delineate developmental trajectories of αβ T cell subsets and refine the kinetic selection model of CD4
    MeSH term(s) Animals ; Cell Differentiation ; Epigenomics ; Humans ; Mice ; Receptors, Antigen, T-Cell, alpha-beta/genetics ; Receptors, Antigen, T-Cell, gamma-delta/genetics ; T-Lymphocyte Subsets ; Transcriptome
    Chemical Substances Receptors, Antigen, T-Cell, alpha-beta ; Receptors, Antigen, T-Cell, gamma-delta
    Language English
    Publishing date 2020-12-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2020.11.014
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  6. Article ; Online: The curious case of a cryptic Cryptosporidium and a missing dendritic cell subset.

    Lee, Donguk / Huseby, Eric S / Gowthaman, Uthaman

    Trends in parasitology

    2021  Volume 38, Issue 2, Page(s) 101–103

    Abstract: Animal models for studying immune responses to Cryptosporidium, a parasite that causes gastrointestinal disease, have been a challenge due to the parasite's poor infectivity in mice. Russler-Germain et al. discovered a 'commensal' strain of ... ...

    Abstract Animal models for studying immune responses to Cryptosporidium, a parasite that causes gastrointestinal disease, have been a challenge due to the parasite's poor infectivity in mice. Russler-Germain et al. discovered a 'commensal' strain of Cryptosporidium, capable of stable infection and vertical transmission, that elicits a T helper type 1 (Th1) response to promote intestinal homeostasis.
    MeSH term(s) Animals ; Cryptosporidiosis/parasitology ; Cryptosporidium ; Dendritic Cells/immunology ; Homeostasis ; Intestines/parasitology ; Mice
    Language English
    Publishing date 2021-12-22
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 2036227-4
    ISSN 1471-5007 ; 1471-4922
    ISSN (online) 1471-5007
    ISSN 1471-4922
    DOI 10.1016/j.pt.2021.12.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  7. Article ; Online: Killer T cells with a beta-flavi(r) for dengue.

    Blevins, Sydney / Huseby, Eric S

    Nature immunology

    2017  Volume 18, Issue 11, Page(s) 1186–1188

    MeSH term(s) Dengue ; Dengue Virus ; Germ Cells ; Humans ; Serogroup ; T-Lymphocytes, Cytotoxic
    Language English
    Publishing date 2017-10-11
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/ni.3833
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  8. Article ; Online: I-A

    Stadinski, Brian D / Cleveland, Sarah B / Brehm, Michael A / Greiner, Dale L / Huseby, Priya G / Huseby, Eric S

    Nature immunology

    2023  Volume 24, Issue 4, Page(s) 652–663

    Abstract: Genetic susceptibility to type 1 diabetes is associated with homozygous expression of major histocompatibility complex class II alleles that carry specific beta chain polymorphisms. Why heterozygous expression of these major histocompatibility complex ... ...

    Abstract Genetic susceptibility to type 1 diabetes is associated with homozygous expression of major histocompatibility complex class II alleles that carry specific beta chain polymorphisms. Why heterozygous expression of these major histocompatibility complex class II alleles does not confer a similar predisposition is unresolved. Using a nonobese diabetic mouse model, here we show that heterozygous expression of the type 1 diabetes-protective allele I-A
    MeSH term(s) Mice ; Animals ; Diabetes Mellitus, Type 1 ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; Histocompatibility Antigens Class II ; Insulin/metabolism ; Mice, Inbred NOD
    Chemical Substances Histocompatibility Antigens Class II ; Insulin
    Language English
    Publishing date 2023-02-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/s41590-023-01441-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  9. Article ; Online: Indoctrinating T cells to attack pathogens through homeschooling.

    Parello, Caitlin S / Huseby, Eric S

    Trends in immunology

    2015  Volume 36, Issue 6, Page(s) 337–343

    Abstract: Adaptive immunity is predicated on the ability of the T cell repertoire to have pre-existing specificity for the universe of potential pathogens. Recent findings suggest that T cell receptor (TCR)-self-major histocompatibility protein (pMHC) interactions ...

    Abstract Adaptive immunity is predicated on the ability of the T cell repertoire to have pre-existing specificity for the universe of potential pathogens. Recent findings suggest that T cell receptor (TCR)-self-major histocompatibility protein (pMHC) interactions limit autoimmune responses while enhancing T cell response to foreign antigens. We review these findings here, placing them in context of the current understanding of how TCR-self-pMHC interactions regulate T cell activation thresholds, and suggest that TCR-self-pMHC interactions increase the efficiency of the T cell repertoire by giving a competitive advantage to peptide cross-reactive T cells. We propose that self-reactivity and peptide cross-reactivity are controlled by particular CDR3 sequence motifs, which would allow thymic selection to contribute to solving the feat of broad pathogen specificity by exporting T cells that are pre-screened by positive and negative selection for the ability to be 'moderately' peptide cross-reactive.
    MeSH term(s) Adaptive Immunity/immunology ; Animals ; Antigen-Presenting Cells/immunology ; Autoimmunity/immunology ; Humans ; Major Histocompatibility Complex/immunology ; Models, Immunological ; Peptides/immunology ; Receptors, Antigen, T-Cell/immunology ; T-Lymphocytes/immunology
    Chemical Substances Peptides ; Receptors, Antigen, T-Cell
    Language English
    Publishing date 2015-06
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2036831-8
    ISSN 1471-4981 ; 1471-4906
    ISSN (online) 1471-4981
    ISSN 1471-4906
    DOI 10.1016/j.it.2015.04.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  10. Article ; Online: CD4 Effector TCR Avidity for Peptide on APC Determines the Level of Memory Generated.

    Jones, Michael C / Castonguay, Catherine / Nanaware, Padma P / Weaver, Grant C / Stadinski, Brian / Kugler-Umana, Olivia A / Huseby, Eric S / Stern, Lawrence J / McKinstry, Karl Kai / Strutt, Tara M / Devarajan, Priyadharshini / Swain, Susan L

    Journal of immunology (Baltimore, Md. : 1950)

    2023  Volume 210, Issue 12, Page(s) 1950–1961

    Abstract: Initial TCR affinity for peptide Ag is known to impact the generation of memory; however, its contributions later, when effectors must again recognize Ag at 5-8 d postinfection to become memory, is unclear. We examined whether the effector TCR affinity ... ...

    Abstract Initial TCR affinity for peptide Ag is known to impact the generation of memory; however, its contributions later, when effectors must again recognize Ag at 5-8 d postinfection to become memory, is unclear. We examined whether the effector TCR affinity for peptide at this "effector checkpoint" dictates the extent of memory and degree of protection against rechallenge. We made an influenza A virus nucleoprotein (NP)-specific TCR transgenic mouse strain, FluNP, and generated NP-peptide variants that are presented by MHC class II to bind to the FluNP TCR over a broad range of avidity. To evaluate the impact of avidity in vivo, we primed naive donor FluNP in influenza A virus-infected host mice, purified donor effectors at the checkpoint, and cotransferred them with the range of peptides pulsed on activated APCs into second uninfected hosts. Higher-avidity peptides yielded higher numbers of FluNP memory cells in spleen and most dramatically in lung and draining lymph nodes and induced better protection against lethal influenza infection. Avidity determined memory cell number, not cytokine profile, and already impacted donor cell number within several days of transfer. We previously found that autocrine IL-2 production at the checkpoint prevents default effector apoptosis and supports memory formation. Here, we find that peptide avidity determines the level of IL-2 produced by these effectors and that IL-2Rα expression by the APCs enhances memory formation, suggesting that transpresentation of IL-2 by APCs further amplifies IL-2 availability. Secondary memory generation was also avidity dependent. We propose that this regulatory pathway selects CD4 effectors of highest affinity to progress to memory.
    MeSH term(s) Mice ; Animals ; CD4-Positive T-Lymphocytes/metabolism ; Interleukin-2/metabolism ; Peptides/metabolism ; Mice, Transgenic ; Receptors, Antigen, T-Cell/metabolism ; Immunologic Memory ; Mice, Inbred C57BL
    Chemical Substances Interleukin-2 ; Peptides ; Receptors, Antigen, T-Cell
    Language English
    Publishing date 2023-10-30
    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.2200337
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top