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  1. Article ; Online: The Entangled World of Memory T Cells and Implications in Transplantation.

    Alexander, Katie L / Ford, Mandy L

    Transplantation

    2023  Volume 108, Issue 1, Page(s) 137–147

    Abstract: Memory T cells that are specific for alloantigen can arise from a variety of stimuli, ranging from direct allogeneic sensitization from prior transplantation, blood transfusion, or pregnancy to the elicitation of pathogen-specific T cells that are cross- ... ...

    Abstract Memory T cells that are specific for alloantigen can arise from a variety of stimuli, ranging from direct allogeneic sensitization from prior transplantation, blood transfusion, or pregnancy to the elicitation of pathogen-specific T cells that are cross-reactive with alloantigen. Regardless of the mechanism by which they arise, alloreactive memory T cells possess key metabolic, phenotypic, and functional properties that render them distinct from naive T cells. These properties affect the immune response to transplantation in 2 important ways: first, they can alter the speed, location, and effector mechanisms with which alloreactive T cells mediate allograft rejection, and second, they can alter T-cell susceptibility to immunosuppression. In this review, we discuss recent developments in understanding these properties of memory T cells and their implications for transplantation.
    MeSH term(s) Memory T Cells ; Graft Rejection/prevention & control ; Transplantation, Homologous ; Skin Transplantation ; Isoantigens ; Immunologic Memory
    Chemical Substances Isoantigens
    Language English
    Publishing date 2023-12-13
    Publishing country United States
    Document type Review ; Journal Article
    ZDB-ID 208424-7
    ISSN 1534-6080 ; 0041-1337
    ISSN (online) 1534-6080
    ISSN 0041-1337
    DOI 10.1097/TP.0000000000004647
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: TOXic signaling: How antigen accelerates T cell exhaustion during transplantation.

    Ford, Mandy L

    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

    2020  Volume 20, Issue 9, Page(s) 2303–2304

    MeSH term(s) Graft Rejection ; Transplantation Tolerance
    Language English
    Publishing date 2020-06-11
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 2060594-8
    ISSN 1600-6143 ; 1600-6135
    ISSN (online) 1600-6143
    ISSN 1600-6135
    DOI 10.1111/ajt.16060
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Differential induction of donor-reactive Foxp3

    Liu, Danya / Yao, Hongmin / Ferrer, Ivana R / Ford, Mandy L

    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

    2024  

    Abstract: Recently published studies in both murine models and a meta-analysis of non-human primate renal transplant studies showed that anti-CD154 reagents conferred a significant survival advantage over CD40 blockers in both animal models and across multiple ... ...

    Abstract Recently published studies in both murine models and a meta-analysis of non-human primate renal transplant studies showed that anti-CD154 reagents conferred a significant survival advantage over CD40 blockers in both animal models and across multiple organs. Here we sought to compare the induction of donor-reactive forkhead box P3+-induced regulatory T cells (Foxp3
    Language English
    Publishing date 2024-03-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2060594-8
    ISSN 1600-6143 ; 1600-6135
    ISSN (online) 1600-6143
    ISSN 1600-6135
    DOI 10.1016/j.ajt.2024.03.033
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Coronin-1, King of Alloimmunity.

    Ford, Mandy L

    Immunity

    2019  Volume 50, Issue 1, Page(s) 3–5

    Abstract: Defining pathways that differentially regulate graft-reactive versus anti-microbial T cell responses could facilitate more precise manipulation of immune responses in the context of organ and tissue transplantation. Here, Jayachandran et al. (2019) ... ...

    Abstract Defining pathways that differentially regulate graft-reactive versus anti-microbial T cell responses could facilitate more precise manipulation of immune responses in the context of organ and tissue transplantation. Here, Jayachandran et al. (2019) identify a coronin-1-PDE4-cAMP axis that, when perturbed, results in the induction of transplantation tolerance while maintaining anti-microbial immunity.
    MeSH term(s) Immunity ; Microfilament Proteins/immunology ; Signal Transduction ; T-Lymphocytes ; Transplantation Tolerance
    Chemical Substances Microfilament Proteins ; coronin proteins (145420-64-0)
    Language English
    Publishing date 2019-01-16
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2018.12.030
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Time for increased awareness of sex as a biological variable in transplantation.

    Ford, Mandy L / Mannon, Roslyn B

    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

    2021  Volume 21, Issue 10, Page(s) 3215–3216

    MeSH term(s) Graft Rejection
    Language English
    Publishing date 2021-07-12
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 2060594-8
    ISSN 1600-6143 ; 1600-6135
    ISSN (online) 1600-6143
    ISSN 1600-6135
    DOI 10.1111/ajt.16733
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Cancer and sepsis.

    Williams, Jeroson C / Ford, Mandy L / Coopersmith, Craig M

    Clinical science (London, England : 1979)

    2023  Volume 137, Issue 11, Page(s) 881–893

    Abstract: Sepsis is one of the leading causes of death worldwide. While mortality is high regardless of inciting infection or comorbidities, mortality in patients with cancer and sepsis is significantly higher than mortality in patients with sepsis without cancer. ...

    Abstract Sepsis is one of the leading causes of death worldwide. While mortality is high regardless of inciting infection or comorbidities, mortality in patients with cancer and sepsis is significantly higher than mortality in patients with sepsis without cancer. Cancer patients are also significantly more likely to develop sepsis than the general population. The mechanisms underlying increased mortality in cancer and sepsis patients are multifactorial. Cancer treatment alters the host immune response and can increase susceptibility to infection. Preclinical data also suggests that cancer, in and of itself, increases mortality from sepsis with dysregulation of the adaptive immune system playing a key role. Further, preclinical data demonstrate that sepsis can alter subsequent tumor growth while tumoral immunity impacts survival from sepsis. Checkpoint inhibition is a well-accepted treatment for many types of cancer, and there is increasing evidence suggesting this may be a useful strategy in sepsis as well. However, preclinical studies of checkpoint inhibition in cancer and sepsis demonstrate results that could not have been predicted by examining either variable in isolation. As sepsis management transitions from a 'one size fits all' model to a more individualized approach, understanding the mechanistic impact of cancer on outcomes from sepsis represents an important strategy towards delivering on the promise of precision medicine in the intensive care unit.
    MeSH term(s) Humans ; Neoplasms/complications ; Sepsis ; Precision Medicine
    Language English
    Publishing date 2023-06-13
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 206835-7
    ISSN 1470-8736 ; 0301-0538 ; 0009-0360 ; 0143-5221
    ISSN (online) 1470-8736
    ISSN 0301-0538 ; 0009-0360 ; 0143-5221
    DOI 10.1042/CS20220713
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Intersection of FcγRIIB, the microbiome, and checkpoint inhibitors in antitumor immunity.

    Baecher, Kirsten M / Ford, Mandy L

    Cancer immunology, immunotherapy : CII

    2021  Volume 70, Issue 12, Page(s) 3397–3404

    Abstract: Fc receptors (FcRs) and the microbiome are both known to have an effect on the development and progression of cancers. Checkpoint inhibitors are a novel class of therapeutics which are used to combat cancer and are integrally linked to both FcRs and the ... ...

    Abstract Fc receptors (FcRs) and the microbiome are both known to have an effect on the development and progression of cancers. Checkpoint inhibitors are a novel class of therapeutics which are used to combat cancer and are integrally linked to both FcRs and the microbiome. The use of checkpoint inhibitors has grown exponentially over the past decade, although many host factors affect both the efficacy and the safety of these therapeutics. Some of these host factors, including the microbiome and the expression of FcRs, are currently being investigated. Here we discuss the current understanding of FcRs (particularly the inhibitory FcγRIIB) and the microbiome in context of T cell immunity, inflammation, cancer, and checkpoint inhibition.
    MeSH term(s) Animals ; Humans ; Immune Checkpoint Inhibitors/immunology ; Immunotherapy/methods ; Inflammation/immunology ; Microbiota/immunology ; Neoplasms/immunology ; Neoplasms/therapy ; Receptors, Fc/immunology
    Chemical Substances Immune Checkpoint Inhibitors ; Receptors, Fc
    Language English
    Publishing date 2021-07-09
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 195342-4
    ISSN 1432-0851 ; 0340-7004
    ISSN (online) 1432-0851
    ISSN 0340-7004
    DOI 10.1007/s00262-021-03004-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Impact of chronic alcohol exposure on conventional and regulatory murine T cell subsets.

    Paterson, Cameron W / Gutierrez, Melissa B / Coopersmith, Craig M / Ford, Mandy L

    Frontiers in immunology

    2023  Volume 14, Page(s) 1142614

    Abstract: Introduction: Chronic alcohol use poses significant negative consequences to public health and, among its many biologic effects, is associated with significant T cell dysregulation within the adaptive immune system that has yet to be fully characterized. ...

    Abstract Introduction: Chronic alcohol use poses significant negative consequences to public health and, among its many biologic effects, is associated with significant T cell dysregulation within the adaptive immune system that has yet to be fully characterized. Novel, automated strategies for high dimensional flow cytometric analysis of the immune system are rapidly improving researchers' ability to detect and characterize rare cell types.
    Methods: Using a murine model of chronic alcohol ingestion in conjunction with viSNE and CITRUS analysis tools, we performed a machine-driven, exploratory analysis comparing rare splenic subpopulations within the conventional CD4
    Results: While there were no differences in the absolute numbers of bulk CD3
    Discussion: These data provide further resolution into the character of decreased naïve T cell populations known to be present in alcohol exposed mice, as well as describe alterations in effector regulatory T cell phenotypes associated with the pathogenesis of chronic alcohol-induced immune dysfunction.
    MeSH term(s) Mice ; Animals ; CD8-Positive T-Lymphocytes ; T-Lymphocyte Subsets ; T-Lymphocytes, Regulatory ; Ethanol ; Forkhead Transcription Factors/metabolism
    Chemical Substances Ethanol (3K9958V90M) ; Forkhead Transcription Factors
    Language English
    Publishing date 2023-03-17
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1142614
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Memory T follicular helper cells drive donor-specific antibodies independent of memory B cells and primary germinal center and alloantibody formation.

    Zeng, Shan / Crichton, Emma S / Ford, Mandy L / Badell, I Raul

    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

    2023  Volume 23, Issue 10, Page(s) 1511–1525

    Abstract: Human leukocyte antigen antibodies are important immunologic mediators of renal allograft loss and are difficult to control. The inability to permanently eliminate donor-specific antibodies (DSA) is partly due to an incomplete understanding of the ... ...

    Abstract Human leukocyte antigen antibodies are important immunologic mediators of renal allograft loss and are difficult to control. The inability to permanently eliminate donor-specific antibodies (DSA) is partly due to an incomplete understanding of the cellular mechanisms driving alloantibody formation, recurrence, and maintenance. Memory T follicular helper (mTfh) cells rapidly interact with memory B cells upon antigen re-exposure for anamnestic humoral responses, but little is known about Tfh memory in transplantation. We hypothesized that alloreactive mTfh cells form after transplantation and play a critical role in DSA formation following alloantigen re-encounter. To test this hypothesis, we utilized murine skin allograft models to identify and characterize Tfh memory and interrogate its ability to mediate alloantibody responses. We identified alloreactive Tfh memory as a mediator of accelerated humoral alloresponses independent of memory B cells and primary germinal center, or DSA, formation. Furthermore, we demonstrate that mTfh-driven alloantibody formation is susceptible to CD28 costimulation blockade. These findings provide novel insight into a pathologic role for memory Tfh in alloantibody responses and strongly support shifting therapeutic focus from the singular targeting of B cell lineage cells and alloantibodies themselves to multimodal strategies that include inhibition of mTfh cells to treat DSA.
    MeSH term(s) Mice ; Humans ; Animals ; Isoantibodies ; Memory B Cells ; T Follicular Helper Cells ; T-Lymphocytes, Helper-Inducer ; Kidney Transplantation ; Germinal Center ; Immunologic Memory
    Chemical Substances Isoantibodies
    Language English
    Publishing date 2023-06-09
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2060594-8
    ISSN 1600-6143 ; 1600-6135
    ISSN (online) 1600-6143
    ISSN 1600-6135
    DOI 10.1016/j.ajt.2023.06.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Activation and regulation of alloreactive T cell immunity in solid organ transplantation.

    Duneton, Charlotte / Winterberg, Pamela D / Ford, Mandy L

    Nature reviews. Nephrology

    2022  Volume 18, Issue 10, Page(s) 663–676

    Abstract: Transplantation is the only curative treatment for patients with kidney failure but it poses unique immunological challenges that must be overcome to prevent allograft rejection and ensure long-term graft survival. Alloreactive T cells are important ... ...

    Abstract Transplantation is the only curative treatment for patients with kidney failure but it poses unique immunological challenges that must be overcome to prevent allograft rejection and ensure long-term graft survival. Alloreactive T cells are important contributors to graft rejection, and a clearer understanding of the mechanisms by which these cells recognize donor antigens - through direct, indirect or semi-direct pathways - will facilitate their therapeutic targeting. Post-T cell priming rejection responses can also be modified by targeting pathways that regulate T cell trafficking, survival cytokines or innate immune activation. Moreover, the quantity and quality of donor-reactive memory T cells crucially shape alloimmune responses. Of note, many fundamental concepts in transplant immunology have been derived from models of infection. However, the programmed differentiation of allograft-specific T cell responses is probably distinct from that of pathogen-elicited responses, owing to the dearth of pathogen-derived innate immune activation in the transplantation setting. Understanding the fundamental (and potentially unique) immunological pathways that lead to allograft rejection is therefore a prerequisite for the rational development of therapeutics that promote transplantation tolerance.
    MeSH term(s) Cytokines ; Graft Rejection/prevention & control ; Humans ; Lymphocyte Activation ; Organ Transplantation ; Transplantation, Homologous
    Chemical Substances Cytokines
    Language English
    Publishing date 2022-07-27
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2490366-8
    ISSN 1759-507X ; 1759-5061
    ISSN (online) 1759-507X
    ISSN 1759-5061
    DOI 10.1038/s41581-022-00600-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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