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Acute gastrointestinal infection induces long-lived microbiota-specific T cell responses.

ABSTRACT: The mammalian gastrointestinal tract contains a large and diverse population of commensal bacteria and is also one of the primary sites of exposure to pathogens. How the immune system perceives commensals in the context of mucosal infection is unclear. Here, we show that during a gastrointestinal infection, tolerance to commensals is lost, and microbiota-specific T cells are activated and differentiate to inflammatory effector cells. Furthermore, these T cells go on to form memory cells that are phenotypically and functionally consistent with pathogen-specific T cells. Our results suggest that during a gastrointestinal infection, the immune response to commensals parallels the immune response against pathogenic microbes and that adaptive responses against commensals are an integral component of mucosal immunity.

SUBMITTER: Hand TW

PROVIDER: S-EPMC3784339 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Acute gastrointestinal infection induces long-lived microbiota-specific T cell responses.

Hand Timothy W TW Dos Santos Liliane M LM Bouladoux Nicolas N Molloy Michael J MJ Pagán Antonio J AJ Pepper Marion M Maynard Craig L CL Elson Charles O CO Belkaid Yasmine Y

Science (New York, N.Y.) 20120823 6101

The mammalian gastrointestinal tract contains a large and diverse population of commensal bacteria and is also one of the primary sites of exposure to pathogens. How the immune system perceives commensals in the context of mucosal infection is unclear. Here, we show that during a gastrointestinal infection, tolerance to commensals is lost, and microbiota-specific T cells are activated and differentiate to inflammatory effector cells. Furthermore, these T cells go on to form memory cells that are ...[more]

PMID: 22923434

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Project description:Multiple lines of evidence indicate that CD8 + T cells are important in the control of HIV-1 (HIV) replication. However, CD8 + T cells induced by natural infection cannot eliminate the virus or reduce viral loads to acceptably low levels in most infected individuals. Understanding the basic quantitative features of CD8 + T-cell responses induced during HIV infection may therefore inform us about the limits that HIV vaccines, which aim to induce protective CD8 + T-cell responses, must exceed. Using previously published experimental data from a cohort of HIV-infected individuals with sampling times from acute to chronic infection we defined the quantitative properties of CD8 + T-cell responses to the whole HIV proteome. In contrast with a commonly held view, we found that the relative number of HIV-specific CD8 + T-cell responses (response breadth) changed little over the course of infection (first 400 days post-infection), with moderate but statistically significant changes occurring only during the first 35 symptomatic days. This challenges the idea that a change in the T-cell response breadth over time is responsible for the slow speed of viral escape from CD8 + T cells in the chronic infection. The breadth of HIV-specific CD8 + T-cell responses was not correlated with the average viral load for our small cohort of patients. Metrics of relative immunodominance of HIV-specific CD8 + T-cell responses such as Shannon entropy or the Evenness index were also not significantly correlated with the average viral load. Our mathematical-model-driven analysis suggested extremely slow expansion kinetics for the majority of HIV-specific CD8 + T-cell responses and the presence of intra- and interclonal competition between multiple CD8 + T-cell responses; such competition may limit the magnitude of CD8 + T-cell responses, specific to different epitopes, and the overall number of T-cell responses induced by vaccination. Further understanding of mechanisms underlying interactions between the virus and virus-specific CD8 + T-cell response will be instrumental in determining which T-cell-based vaccines will induce T-cell responses providing durable protection against HIV infection.

Dataset Information

Acute gastrointestinal infection induces long-lived microbiota-specific T cell responses.

Publications

Acute gastrointestinal infection induces long-lived microbiota-specific T cell responses.

Similar Datasets

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