Understanding and overcoming the barriers to T cell-mediated immunity against tuberculosis.

TitleUnderstanding and overcoming the barriers to T cell-mediated immunity against tuberculosis.
Publication TypeJournal Article
Year of Publication2014
AuthorsUrdahl KB
JournalSemin Immunol
Volume26
Issue6
Pagination578-87
Date Published2014 Dec
ISSN1096-3618
KeywordsAnimals, Cytokines, Humans, Immune Evasion, Immunity, Cellular, Immunologic Memory, Lung, Lymphocyte Activation, Macrophages, Alveolar, Mice, Mycobacterium tuberculosis, T-Lymphocytes, Time Factors, Tuberculosis Vaccines, Tuberculosis, Pulmonary
Abstract

Despite the overwhelming success of immunization in reducing, and even eliminating, the global threats posed by a wide spectrum of infectious diseases, attempts to do the same for tuberculosis (TB) have failed to date. While most effective vaccines act by eliciting neutralizing antibodies, T cells are the primary mediators of adaptive immunity against TB. Unfortunately, the onset of the T cell response after aerosol infection with Mycobacterium tuberculosis (Mtb), the bacterium that causes TB, is exceedingly slow, and systemically administered vaccines only modestly accelerate the recruitment of effector T cells to the lungs. This delay seems to be orchestrated by Mtb itself to prolong the period of unrestricted bacterial replication in the lung that characterizes the innate phase of the response. When T cells finally arrive at the site of infection, multiple layers of regulation have been established that limit the ability of T cells to control or eradicate Mtb. From this understanding, emerges a strategy for achieving immunity. Lung resident memory T cells may recognize Mtb-infected cells shortly after infection and confer protection before regulatory networks are allowed to develop. Early studies using vaccines that elicit lung resident T cells by targeting the lung mucosa have been promising, but many questions remain. Due to the fundamental nature of these questions, and the need to understand and manipulate the early events in the lung after aerosol infection, only coordinated approaches that utilize tractable animal models to inform human TB vaccine trials will move the field toward its goal.

DOI10.1016/j.smim.2014.10.003
Alternate JournalSemin. Immunol.
PubMed ID25453230
PubMed Central IDPMC4314386
Grant ListR01 AI076327 / AI / NIAID NIH HHS / United States
U19 AI106761 / AI / NIAID NIH HHS / United States
AI076327 / AI / NIAID NIH HHS / United States
AI106761 / AI / NIAID NIH HHS / United States