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Principal Investigator: Cody Welford Thompson
Organization: UNIVERSITY OF NORTH CAROLINA CHARLOTTE
Fiscal Year: 2024
Award: $470,518
Funding agency: National Institute of Allergy and Infectious Diseases
Project Summary/Abstract
Without T cells (e.g., CD4+ helper, CD8+ cytotoxic), mammals cannot have a proper functioning immune
system or fight off viral infection. Classically, T cells in mammals develop in the thymus then migrate to
peripheral tissues and circulate in the blood. Development of T cells is critical for mounting antiviral response
cytokines, immune memory, regulation, pathogen recognition, activation of B-cells to produce antibodies, and
cytotoxic response to virus-infected cells. Bats are able to suppress the most highly pathogenic viruses found
in mammals (e.g., SARS, Ebola, Rabies, and Nipah) with little to no clinical symptoms or pathology acting as
the main reservoir. Yet after 100 years of anatomical study little is known about T cell development,
abundance, expression, or T-cell receptors (TCRs) repertoire within bats. Studies of bat T cell development
and responses in bats have largely been understudied due to lack of immunological reagents such as
antibodies specific for bats.
In this resubmission, our research team has provided preliminary data using x-ray computed
tomography, histology, and immunohistochemistry that bats have thymus with T cells present. We also provide
evidence of age related thymus involution within adult big brown bats (Eptesicus fuscus). In our proposal, we
will use museum voucher specimens and collect wild bats to further develop methods for structural and
molecular approaches to study lymphoid organs and T cell development.
Our team has decades of experience in mammalogy, viral-host interaction, adaptive immune system
sequencing (VDJseq), and viral immunology. We will provide ultrastructural determination of the bat’s thymus,
spleen, lymph ducts, and bone marrow that will include development of antibodies for flow cytometry/FACS or
mRNA based in situ hybridization flow cytometry (Flow-FISH), single molecule fluorescence mRNA in situ
hybridization (mRNA-smFISH) and immunohistochemistry (which we have preliminary data) that will elucidate
the lymphoid organs of T cell development (Aim 1). In Aim 2, we will assess T cell development in bat primary
and secondary lymphoid organs across developmental age (juveniles, subadults, and adults) and examine
sexual dimorphism, using bulk organ RNAseq, single cell RNAseq, and RT-ddPCR. Using VDJseq/TCRseq we
will measure the TCR repertoire diversity across lymphoid tissues and blood (Aim 2). In Aim 3, we will access
and link thymic involution to the susceptibility of bats to pathogenic viruses.
Our proposal and team is uniquely posed to provide a new path towards unraveling the ‘black box’ of
bat T cell adaptive immune responses. This is foundational work that will enable further immunological study in
bats and other small mammals but provide a groundwork to new immunotherapies, vaccines, antivirals, or
anti-inflammatory drugs.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><21+ years old><Adaptive Immune System><Address><Adolescent><Adolescent Youth><Adult><Adult Human><Age><American><Anatomic Sites><Anatomic structures><Anatomy><Animals><Anti-Inflammatories><Anti-Inflammatory Agents><Anti-inflammatory><Anti-viral Agents><Anti-viral Response><Antibodies><Antibody Repertoire><B-Cell Activation><B-Cell Development><Bats><Biology><Black Box><Blood><Blood Reticuloendothelial System><Body Tissues><Bone Marrow><Bone Marrow Reticuloendothelial System><CAT scan><CD4 Cells><CD4 Positive T Lymphocytes><CD4 T cells><CD4 helper T cell><CD4 lymphocyte><CD4+ T-Lymphocyte><CD4-Positive Lymphocytes><CD8><CD8B><CD8B1><CD8B1 gene><COVID crisis><COVID epidemic><COVID pandemic><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 virus><COVID-19 years><COVID19 virus><CT X Ray><CT Xray><CT imaging><CT scan><Cell Body><Cell Maturation><Cells><Cessation of life><Chiroptera><Clinical><CoV-2><CoV2><Computed Tomography><Coronaviridae><Coronavirus><DNA Recombination><Data><Death><Development><Drugs><Earth><Ebola><Education and Training><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Fluorescence><Frankfurt-Marburg Syndrome Virus><Genes><Genetic Recombination><Goals><Health><Henipavirus><Histologic><Histologically><Histology><Home><Image><Immune><Immune mediated therapy><Immune memory><Immune system><Immunes><Immunity><Immunochemical Immunologic><Immunohistochemistry><Immunohistochemistry Cell/Tissue><Immunohistochemistry Staining Method><Immunologic><Immunologic Memory><Immunological><Immunological Memory><Immunologically><Immunologically Directed Therapy><Immunologics><Immunology><Immunotherapy><In Situ Hybridization><Infection><Knowledge><LYT3><Laboratories><Link><Location><Lymph Node Reticuloendothelial System><Lymph node proper><Lymphatic Tissue><Lymphatic nodes><Lymphoid Tissue><Mammalia><Mammals><Marburg><Marburg virus><Marburg-like Viruses><Marburgvirus><Measures><Mediating><Medication><Messenger RNA><Methods><Molecular><Museums><Nipah><Organ><Organism><Pathogenicity><Pathology><Peripheral><Pharmaceutical Preparations><Planet Earth><Predisposition><Process><Progenitor Cells><RNA Seq><RNA Viruses><RNA sequencing><RNAseq><Rabies><Reagent><Recombination><Regulation><Research><Research Specimen><Role><SARS><SARS corona virus 2><SARS coronavirus disease><SARS-CO-V2><SARS-COVID-2><SARS-CoV disease><SARS-CoV-2><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-CoV2><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Scientist><Sentinel><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe Acute Respiratory Syndrome CoV disease><Severe Acute Respiratory Syndrome coronavirus disease><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome related corona virus 2><Site><Specialist><Specimen><Spleen><Spleen Reticuloendothelial System><Structure><Susceptibility><Symptoms><T cell receptor repertoire sequencing><T cell receptor sequencing><T-Cell Development><T-Cell Ontogeny><T-Cells><T-Lymphocyte><T-Lymphocyte Development><T-cell receptor repertoire><T4 Cells><T4 Lymphocytes><TCR repertoire><TCR repertoire sequencing><TCR sequencing><TCR-seq><TCRseq><Techniques><Testing><Thymus><Thymus Gland><Thymus Proper><Thymus Reticuloendothelial System><Tissues><Tomodensitometry><Training><Training and Education><Vaccines><Viral><Viral Diseases><Virus><Virus Diseases><Visualization software><Work><Wuhan coronavirus><X-Ray CAT Scan><X-Ray Computed Tomography><X-Ray Computerized Tomography><Xray CAT scan><Xray Computed Tomography><Xray computerized tomography><acquired immune system><activated B cells><adaptive immune response><adaptive immunity><adulthood><age associated><age correlated><age dependent><age linked><age related><age specific><ages><analytical tool><anamnestic reaction><anti-viral compound><anti-viral drugs><anti-viral immunity><anti-viral medication><anti-viral therapeutic><anti-virals><antiviral immunity><catscan><computed axial tomography><computer tomography><computerized axial tomography><computerized tomography><corona virus><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease 2019 virus><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><coronavirus disease-19 virus><cytokine><cytotoxic><cytotoxic CD8 T cells><cytotoxic CD8 T lymphocyte><developmental><drug/agent><experience><fighting><flow cytophotometry><hCoV19><homes><imaging><immune system function><immune therapeutic approach><immune therapeutic interventions><immune therapeutic regimens><immune therapeutic strategy><immune therapy><immune-based therapies><immune-based treatments><immuno therapy><in situ Hybridization Genetics><in situ Hybridization Staining Method><insight><juvenile><juvenile human><life span><lifespan><living system><lymph duct><lymph gland><lymph nodes><lymph organ><lymphatic duct><lymphatic organ><lymphnodes><lymphoid organ><lyssa><mRNA><migration><multiomics><multiple omics><nCoV2><next generation><non-contrast CT><noncontrast CT><noncontrast computed tomography><panomics><pathogen><pathogenic virus><primary lymphatic organ><primary lymphoid organ><programs><response><scRNA-seq><secondary immune response><secondary lymph organ><secondary lymphatic organ><secondary lymphoid organ><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><sex><sex dimorphism><sexual dimorphism><sexually dimorphic><single cell RNA-seq><single cell RNAseq><single cell expression profiling><single cell transcriptomic profiling><single molecule><single-cell RNA sequencing><social role><stem cells><thymus derived lymphocyte><transcriptome sequencing><transcriptomic sequencing><undergrad><undergraduate><undergraduate student><viral infection><viral pathogen><virology><virus infection><virus pathogen><virus-induced disease><visualization tool><voucher>