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Mucosal memory CD8? T cells are selected in the periphery by an MHC class I molecule.

ABSTRACT: The presence of immune memory at pathogen-entry sites is a prerequisite for protection. Nevertheless, the mechanisms that warrant immunity at peripheral interfaces are not understood. Here we show that the nonclassical major histocompatibility complex (MHC) class I molecule thymus leukemia antigen (TL), induced on dendritic cells interacting with CD8?? on activated CD8??(+) T cells, mediated affinity-based selection of memory precursor cells. Furthermore, constitutive expression of TL on epithelial cells led to continued selection of mature CD8??(+) memory T cells. The memory process driven by TL and CD8?? was essential for the generation of CD8??(+) memory T cells in the intestine and the accumulation of highly antigen-sensitive CD8??(+) memory T cells that form the first line of defense at the largest entry port for pathogens.

SUBMITTER: Huang Y

PROVIDER: S-EPMC3197978 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Mucosal memory CD8⁺ T cells are selected in the periphery by an MHC class I molecule.

Huang Yujun Y Park Yunji Y Wang-Zhu Yiran Y Larange Alexandre A Arens Ramon R Bernardo Iván I Olivares-Villagómez Danyvid D Herndler-Brandstetter Dietmar D Abraham Ninan N Grubeck-Loebenstein Beatrix B Schoenberger Stephen P SP Van Kaer Luc L Kronenberg Mitchell M Teitell Michael A MA Cheroutre Hilde H

Nature immunology 20111002 11

The presence of immune memory at pathogen-entry sites is a prerequisite for protection. Nevertheless, the mechanisms that warrant immunity at peripheral interfaces are not understood. Here we show that the nonclassical major histocompatibility complex (MHC) class I molecule thymus leukemia antigen (TL), induced on dendritic cells interacting with CD8αα on activated CD8αβ(+) T cells, mediated affinity-based selection of memory precursor cells. Furthermore, constitutive expression of TL on epithel ...[more]

PMID: 21964609

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Project description:Following infection of the central nervous system (CNS), the immune system is faced with the challenge of eliminating the pathogen without causing significant damage to neurons, which have limited capacities of renewal. In particular, it was thought that neurons were protected from direct attack by cytotoxic T lymphocytes (CTL) because they do not express major histocompatibility class I (MHC I) molecules, at least at steady state. To date, most of our current knowledge on the specifics of neuron-CTL interaction is based on studies artificially inducing MHC I expression on neurons, loading them with exogenous peptide and applying CTL clones or lines often differentiated in culture. Thus, much remains to be uncovered regarding the modalities of the interaction between infected neurons and antiviral CD8 T cells in the course of a natural disease. Here, we used the model of neuroinflammation caused by neurotropic Borna disease virus (BDV), in which virus-specific CTL have been demonstrated as the main immune effectors triggering disease. We tested the pathogenic properties of brain-isolated CD8 T cells against pure neuronal cultures infected with BDV. We observed that BDV infection of cortical neurons triggered a significant up regulation of MHC I molecules, rendering them susceptible to recognition by antiviral CTL, freshly isolated from the brains of acutely infected rats. Using real-time imaging, we analyzed the spatio-temporal relationships between neurons and CTL. Brain-isolated CTL exhibited a reduced mobility and established stable contacts with BDV-infected neurons, in an antigen- and MHC-dependent manner. This interaction induced rapid morphological changes of the neurons, without immediate killing or impairment of electrical activity. Early signs of neuronal apoptosis were detected only hours after this initial contact. Thus, our results show that infected neurons can be recognized efficiently by brain-isolated antiviral CD8 T cells and uncover the unusual modalities of CTL-induced neuronal damage.

Dataset Information

Mucosal memory CD8? T cells are selected in the periphery by an MHC class I molecule.

Publications

Mucosal memory CD8⁺ T cells are selected in the periphery by an MHC class I molecule.

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