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Immunity to Tuberculosis. It is estimated that 1/3 of the world’s population has been infected with Mycobacterium tuberculosis (Mtb). In the majority of infected people, the immune response is able to adequately control the infection, and consequently only 5-10% will develop clinical disease during their lifetime. My long-term goal is to understand the immunological basis for protective immunity. One way we are investigating this problem is to determine why different mouse strains differ in their susceptibility to tuberculosis. We have observed that certain susceptible mouse strains are unable to efficiently recruit T cells to the lung following infection with Mtb, and this failure likely contributes to increased mortality and morbidity of susceptible mice. Therefore, we are particularly interested in the early events leading to the initiation of the pulmonary immune response following respiratory Mtb infection. This includes establishing how T cells and myeloid cells are recruited back to the lung and how these cells mediate their effector functions.

Although BCG is used universally as a vaccine, its efficacy in preventing pulmonary tuberculosis is controversial. Most Mtb infected individuals develop long-lived immunity that contains the infection in a T cell-dependent manner. Thus, there is considerable interest in how different T cell subsets contribute to immunity and whether vaccination can stimulate protective T cells. Delineating the role of CD8+ T cells in host immunity to Mtb has been hindered by the paucity of antigens known to be recognized by CD8+ T cells. Our antigen discovery program has successfully identified and defined several mycobacterial peptide epitopes that are recognized by CD8+ T cells. For example, CD8+ T cells specific for culture filtrate protein-10 (CFP10) are found in infected people, indicating that CFP10 can prime CD8+ T cells after infection. Notably, CFP10 is encoded in the RD1 genetic locus, which is associated with Mtb virulence. The aim of our studies is to identify, enumerate and functionally characterize antigen-specific CD8+ T cells that are elicited following pulmonary infection. Finally, we are determining whether these antigens can be used as vaccines to elicit protective immunity.

One or more keywords matched the following items that are connected to Behar, Samuel
Item TypeName
Academic Article Conservation of a CD1 multigene family in the guinea pig.
Academic Article OP-1 enhances dendritic growth from cerebral cortical neurons in vitro.
Academic Article Dissemination of Mycobacterium tuberculosis is influenced by host factors and precedes the initiation of T-cell immunity.
Academic Article Conservation of CD1 intracellular trafficking patterns between mammalian species.
Academic Article Diverse TCRs recognize murine CD1.
Academic Article Structural features of the acyl chain determine self-phospholipid antigen recognition by a CD1d-restricted invariant NKT (iNKT) cell.
Academic Article Lysosomal localization of murine CD1d mediated by AP-3 is necessary for NK T cell development.
Academic Article Expression of CD1d2 on thymocytes is not sufficient for the development of NK T cells in CD1d1-deficient mice.
Academic Article Susceptibility of mice deficient in CD1D or TAP1 to infection with Mycobacterium tuberculosis.
Academic Article Cytolytic CD8+ T cells recognizing CFP10 are recruited to the lung after Mycobacterium tuberculosis infection.
Academic Article In vivo depletion of CD11c+ cells delays the CD4+ T cell response to Mycobacterium tuberculosis and exacerbates the outcome of infection.
Academic Article Interplay of cytokines and microbial signals in regulation of CD1d expression and NKT cell activation.
Academic Article The LFA-1 adhesion molecule is required for protective immunity during pulmonary Mycobacterium tuberculosis infection.
Academic Article Murine CD1d-restricted T cell recognition of cellular lipids.
Academic Article Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria.
Academic Article Gamma interferon-producing CD4+ T lymphocytes in the lung correlate with resistance to infection with Mycobacterium tuberculosis.
Academic Article Mycobacterium tuberculosis-specific CD8+ T cells and their role in immunity.
Academic Article Bacterial protein secretion is required for priming of CD8+ T cells specific for the Mycobacterium tuberculosis antigen CFP10.
Academic Article Tuberculosis triggers a tissue-dependent program of differentiation and acquisition of effector functions by circulating monocytes.
Academic Article Synovial fibroblasts self-direct multicellular lining architecture and synthetic function in three-dimensional organ culture.
Academic Article Regulation of CD1 function and NK1.1(+) T cell selection and maturation by cathepsin S.
Academic Article Impact of somatic mutation on the S107(T15) heavy-chain V region of antibodies reactive with self and nonself.
Academic Article EspA acts as a critical mediator of ESX1-dependent virulence in Mycobacterium tuberculosis by affecting bacterial cell wall integrity.
Academic Article Development of a glycoprotein D-expressing dominant-negative and replication-defective herpes simplex virus 2 (HSV-2) recombinant viral vaccine against HSV-2 infection in mice.
Academic Article Lipids, apoptosis, and cross-presentation: links in the chain of host defense against Mycobacterium tuberculosis.
Academic Article Critical role for invariant chain in CD1d-mediated selection and maturation of Va14-invariant NKT cells.
Academic Article Recognition of microbial and mammalian phospholipid antigens by NKT cells with diverse TCRs.
Academic Article Dying to live: how the death modality of the infected macrophage affects immunity to tuberculosis.
Academic Article Toll-like receptor 4-defective C3H/HeJ mice are not more susceptible than other C3H substrains to infection with Mycobacterium tuberculosis.
Academic Article Susceptibility to Mycobacterium tuberculosis: lessons from inbred strains of mice.
Academic Article Characterization of somatically mutated S107 VH11-encoded anti-DNA autoantibodies derived from autoimmune (NZB x NZW)F1 mice.
Academic Article The major histocompatibility complex haplotype affects T-cell recognition of mycobacterial antigens but not resistance to Mycobacterium tuberculosis in C3H mice.
Academic Article Primary type II alveolar epithelial cells present microbial antigens to antigen-specific CD4+ T cells.
Academic Article Anamnestic responses of mice following Mycobacterium tuberculosis infection.
Academic Article Antigen-specific CD8+ T cells and the development of central memory during Mycobacterium tuberculosis infection.
Academic Article CD1-restricted T cells in host defense to infectious diseases.
Academic Article Vaccine-elicited 10-kilodalton culture filtrate protein-specific CD8+ T cells are sufficient to mediate protection against Mycobacterium tuberculosis infection.
Academic Article Mycolyltransferase-mediated glycolipid exchange in Mycobacteria.
Academic Article Lipid mediators in innate immunity against tuberculosis: opposing roles of PGE2 and LXA4 in the induction of macrophage death.
Academic Article Mycobacterium tuberculosis-specific CD8+ T cells require perforin to kill target cells and provide protection in vivo.
Academic Article Innate invariant NKT cells recognize Mycobacterium tuberculosis-infected macrophages, produce interferon-gamma, and kill intracellular bacteria.
Academic Article Mycobacterium tuberculosis evades macrophage defenses by inhibiting plasma membrane repair.
Academic Article Vaccine-induced antibody isotypes are skewed by impaired CD4 T cell and invariant NKT cell effector responses in MyD88-deficient mice.
Academic Article Alpha-galactosylceramide as a therapeutic agent for pulmonary Mycobacterium tuberculosis infection.
Academic Article Eicosanoid pathways regulate adaptive immunity to Mycobacterium tuberculosis.
Academic Article Tim3 binding to galectin-9 stimulates antimicrobial immunity.
Academic Article Mycobacterium tuberculosis directs immunofocusing of CD8+ T cell responses despite vaccination.
Academic Article Cardiolipin binds to CD1d and stimulates CD1d-restricted ?d T cells in the normal murine repertoire.
Academic Article Requirement for invariant chain in macrophages for Mycobacterium tuberculosis replication and CD1d antigen presentation.
Academic Article Regulation of neutrophils by interferon-? limits lung inflammation during tuberculosis infection.
Academic Article A comparative lipidomics platform for chemotaxonomic analysis of Mycobacterium tuberculosis.
Academic Article Efferocytosis is an innate antibacterial mechanism.
Academic Article T cells home to the thymus and control infection.
Academic Article Antigen-specific CD8(+) T cells and protective immunity to tuberculosis.
Academic Article IL-1? promotes antimicrobial immunity in macrophages by regulating TNFR signaling and caspase-3 activation.
Concept Mice, Inbred BALB C
Concept Mice, Knockout
Concept Mice, Inbred C3H
Concept Mice
Concept Mice, Inbred C57BL
Concept Mice, Transgenic
Concept Mice, Inbred Strains
Concept Mice, Mutant Strains
Academic Article A novel cell surface antigen (T305) found in increased frequency on acute leukemia cells and in autoimmune disease states.
Academic Article Tryptophan biosynthesis protects mycobacteria from CD4 T-cell-mediated killing.
Academic Article iNKT cell production of GM-CSF controls Mycobacterium tuberculosis.
Academic Article Macrophages clean up: efferocytosis and microbial control.
Academic Article Chromatin decondensation and T cell hyperresponsiveness in diabetes-associated hyperglycemia.
Academic Article Human and Murine Clonal CD8+ T Cell Expansions Arise during Tuberculosis Because of TCR Selection.
Academic Article A Higher Activation Threshold of Memory CD8+ T Cells Has a Fitness Cost That Is Modified by TCR Affinity during Tuberculosis.
Academic Article Multiple Inflammatory Cytokines Converge To Regulate CD8+ T Cell Expansion and Function during Tuberculosis.
Academic Article TIM3 Mediates T Cell Exhaustion during Mycobacterium tuberculosis Infection.
Academic Article Tuberculosis Susceptibility and Vaccine Protection Are Independently Controlled by Host Genotype.
Academic Article IL-21 signaling is essential for optimal host resistance against Mycobacterium tuberculosis infection.
Academic Article Mycobacterium tuberculosis-specific CD4+ and CD8+ T cells differ in their capacity to recognize infected macrophages.
Academic Article Vaccine-elicited memory CD4+ T cell expansion is impaired in the lungs during tuberculosis.
Academic Article Role of Granulocyte-Macrophage Colony-Stimulating Factor Production by T Cells during Mycobacterium tuberculosis Infection.
Academic Article TRAV1-2+ CD8+ T-cells including oligoconal expansions of MAIT cells are enriched in the airways in human tuberculosis.
Academic Article Limited recognition of Mycobacterium tuberculosis-infected macrophages by polyclonal CD4 and CD8 T cells from the lungs of infected mice.
Academic Article Functionally Overlapping Variants Control Tuberculosis Susceptibility in Collaborative Cross Mice.
Academic Article CD11cHi?monocyte-derived macrophages are a major cellular compartment infected by Mycobacterium tuberculosis.
Academic Article A natural polymorphism of Mycobacterium tuberculosis in the esxH gene disrupts immunodomination by the TB10.4-specific CD8 T cell response.
Academic Article CD4 T?cell help prevents CD8 T?cell exhaustion and promotes control of Mycobacterium tuberculosis infection.
Academic Article Mitochondrial respiration contributes to the interferon gamma response in antigen-presenting cells.
Academic Article IFN? and iNOS-Mediated Alterations in the Bone Marrow and Thymus and Its Impact on Mycobacterium avium-Induced Thymic Atrophy.
Concept Mice, 129 Strain
Academic Article Use of the Human Granulysin Transgenic Mice To Evaluate the Role of Granulysin Expression by CD8 T Cells in Immunity To Mycobacterium tuberculosis.
Academic Article High Bacillary Burden and the ESX-1 Type VII Secretion System Promote MHC Class I Presentation by Mycobacterium tuberculosis-Infected Macrophages to CD8 T Cells.
Academic Article Host genetic background is a barrier to broadly effective vaccine-mediated protection against tuberculosis.
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