Chemokine gene expression in lung CD8 T cells correlates with protective immunity in mice immunized intra-nasally with Adenovirus-85A.Reportar como inadecuado




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Reference: Lee, LN, Baban, D, Ronan, EO et al., (2010). Chemokine gene expression in lung CD8 T cells correlates with protective immunity in mice immunized intra-nasally with Adenovirus-85A. BMC medical genomics, 3 (1), 46.Citable link to this page:

 

Chemokine gene expression in lung CD8 T cells correlates with protective immunity in mice immunized intra-nasally with Adenovirus-85A.

Abstract: BACKGROUND: Immunization of BALB/c mice with a recombinant adenovirus expressing Mycobacterium tuberculosis (M. tuberculosis) antigen 85A (Ad85A) protects against aerosol challenge with M. tuberculosis only when it is administered intra-nasally (i.n.). Immunization with Ad85A induces a lung-resident population of activated CD8 T cells that is antigen dependent, highly activated and mediates protection by early inhibition of M. tuberculosis growth. In order to determine why the i.n. route is so effective compared to parenteral immunization, we used microarray analysis to compare gene expression profiles of pulmonary and splenic CD8 T cells after i.n. or intra-dermal (i.d.) immunization. METHOD: Total RNA from CD8 T cells was isolated from lungs or spleens of mice immunized with Ad85A by the i.n. or i.d. route. The gene profiles generated from each condition were compared. Statistically significant (p ≤ 0.05) differentially expressed genes were analyzed to determine if they mapped to particular molecular functions, biological processes or pathways using Gene Ontology and Panther DB mapping tools. RESULTS: CD8 T cells from lungs of i.n. immunized mice expressed a large number of chemokines chemotactic for resting and activated T cells as well as activation and survival genes. Lung lymphocytes from i.n. immunized mice also express the chemokine receptor gene Cxcr6, which is thought to aid long-term retention of antigen-responding T cells in the lungs. Expression of CXCR6 on CD8 T cells was confirmed by flow cytometry. CONCLUSIONS: Our microarray analysis represents the first ex vivo study comparing gene expression profiles of CD8 T cells isolated from distinct sites after immunization with an adenoviral vector by different routes. It confirms earlier phenotypic data indicating that lung i.n. cells are more activated than lung i.d. CD8 T cells. The sustained expression of chemokines and activation genes enables CD8 T cells to remain in the lungs for extended periods after i.n. immunization. This may account for the early inhibition of M. tuberculosis growth observed in Ad85A i.n. immunized mice and explain the effectiveness of i.n. compared to parenteral immunization with this viral vector.

Peer Review status:Peer reviewedPublication status:PublishedVersion:Publisher's version Funder: Medical Research Council   Notes:© 2010 Lee et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Bibliographic Details

Publisher: BioMed Central Ltd.

Publisher Website: http://www.biomedcentral.com/

Journal: BMC medical genomicssee more from them

Publication Website: http://www.biomedcentral.com/bmcmedgenomics/

Issue Date: 2010-10-13

pages:46Identifiers

Urn: uuid:fab0533a-2ef5-4ef7-8e5d-267bc166765c

Source identifier: 90299

Eissn: 1755-8794

Doi: https://doi.org/10.1186/1755-8794-3-46

Issn: 1755-8794 Item Description

Type: Journal article;

Language: eng

Version: Publisher's versionKeywords: Animals Mice, Inbred BALB C Mice Spleen Lung Mycobacterium tuberculosis Adenoviridae CD8-Positive T-Lymphocytes Acyltransferases Chemokines Immunization Administration, Intranasal Biological Markers Antigens, Bacterial Gene Expression Profiling Gene Expression Regulation Injections, Intradermal Female Tiny URL: pubs:90299

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Autor: Lee, LN - institutionUniversity of Oxford - - - Baban, D - institutionUniversity of Oxford - - - Ronan, EO - institutionUniversit

Fuente: https://ora.ox.ac.uk/objects/uuid:fab0533a-2ef5-4ef7-8e5d-267bc166765c



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