title: Orchestration of pulmonary T cell immunity during Mycobacterium tuberculosis infection: immunity interruptus.
abstract: Despite the introduction almost a century ago of Mycobacterium bovis BCG (BCG), an attenuated form of M. bovis that is used as a vaccine against Mycobacterium tuberculosis, tuberculosis remains a global health threat and kills more than 1.5 million people each year. This is mostly because BCG fails to prevent pulmonary disease--the contagious form of tuberculosis. Although there have been significant advances in understanding how the immune system responds to infection, the qualities that define protective immunity against M. tuberculosis remain poorly characterized. The ability to predict who will maintain control over the infection and who will succumb to clinical disease would revolutionize our approach to surveillance, control, and treatment. Here we review the current understanding of pulmonary T cell responses following M. tuberculosis infection. While infection elicits a strong immune response that contains infection, M. tuberculosis evades eradication. Traditionally, its intracellular lifestyle and alteration of macrophage function are viewed as the dominant mechanisms of evasion. Now we appreciate that chronic inflammation leads to T cell dysfunction. While this may arise as the host balances the goals of bacterial sterilization and avoidance of tissue damage, it is becoming clear that T cell dysfunction impairs host resistance. Defining the mechanisms that lead to T cell dysfunction is crucial as memory T cell responses are likely to be subject to the same subject to the same pressures. Thus, success of T cell based vaccines is predicated on memory T cells avoiding exhaustion while at the same time not promoting overt tissue damage.
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655, United States. Electronic address: samuel.behar@umassmed.edu.
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Behar
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655, United States; Millennium Program, Graduate School of Biomedical Sciences, University of Massachusetts Medical School, Worcester, MA 01605, United States; Division of Infectious Disease and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, United States; Division of Infectious Disease, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, United States.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Carpenter
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655, United States; Program in Immunology, Division of Medical Sciences, Harvard Medical School, Boston, MA 02115, United States.
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Booty
authors.affiliation: T Lymphocyte Biology Unit, Laboratory of Parasitic Diseases, NIAID/NIH, Bethesda, MD 20892, United States.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Barber
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655, United States.
authors.forename: Pushpa
authors.initials: P
authors.lastname: Jayaraman
mesh_terms: D056704:Adaptive Immunity; D017951:Antigen Presentation; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D017211:Treatment Failure; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control; D014611:Vaccination
chemical_list: D001500:BCG Vaccine; D016207:Cytokines
keywords: Cytokine; Exhaustion; Memory; Priming; T cell; Tuberculosis