Chemokine Gene Expression in Lung CD8 T Cells Correlates with Protective Immunity in Mice Immunized Intra-nasally with Adenovirus-85A

Overview

Journal BMC Med Genomics

Publisher Biomed Central

Specialty Genetics

Date 2010 Oct 15

PMID 20942964

Citations 8

Authors

Lian N Lee

Dilair Baban

Edward O Ronan

Jiannis Ragoussis

Peter C L Beverley

Elma Z Tchilian

Affiliations

Soon will be listed here.

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.

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References

Reiley W, Calayag M, Wittmer S, Huntington J, Pearl J, Fountain J . ESAT-6-specific CD4 T cell responses to aerosol Mycobacterium tuberculosis infection are initiated in the mediastinal lymph nodes. Proc Natl Acad Sci U S A. 2008; 105(31):10961-6. PMC: 2504808. DOI: 10.1073/pnas.0801496105. View

Marshall D, Olivas E, Andreansky S, La Gruta N, Neale G, Gutierrez A . Effector CD8+ T cells recovered from an influenza pneumonia differentiate to a state of focused gene expression. Proc Natl Acad Sci U S A. 2005; 102(17):6074-9. PMC: 1087947. DOI: 10.1073/pnas.0501960102. View

Huang D, Sherman B, Lempicki R . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009; 4(1):44-57. DOI: 10.1038/nprot.2008.211. View

Liu G, Friggeri A, Yang Y, Park Y, Tsuruta Y, Abraham E . miR-147, a microRNA that is induced upon Toll-like receptor stimulation, regulates murine macrophage inflammatory responses. Proc Natl Acad Sci U S A. 2009; 106(37):15819-24. PMC: 2747202. DOI: 10.1073/pnas.0901216106. View

Gordon Y, Huang L, Romanowski E, Yates K, Proske R, McDermott A . Human cathelicidin (LL-37), a multifunctional peptide, is expressed by ocular surface epithelia and has potent antibacterial and antiviral activity. Curr Eye Res. 2005; 30(5):385-94. PMC: 1497871. DOI: 10.1080/02713680590934111. View

Winslow G, Cooper A, Reiley W, Chatterjee M, Woodland D . Early T-cell responses in tuberculosis immunity. Immunol Rev. 2008; 225:284-99. PMC: 3827678. DOI: 10.1111/j.1600-065X.2008.00693.x. View

Gonzalez-Juarrero M, Kingry L, Ordway D, Henao-Tamayo M, Harton M, Basaraba R . Immune response to Mycobacterium tuberculosis and identification of molecular markers of disease. Am J Respir Cell Mol Biol. 2008; 40(4):398-409. PMC: 2660559. DOI: 10.1165/rcmb.2008-0248OC. View

Ronan E, Ni Lee L, Beverley P, Tchilian E . Immunization of mice with a recombinant adenovirus vaccine inhibits the early growth of Mycobacterium tuberculosis after infection. PLoS One. 2009; 4(12):e8235. PMC: 2785469. DOI: 10.1371/journal.pone.0008235. View

Wang J, Thorson L, Stokes R, Santosuosso M, Huygen K, Zganiacz A . Single mucosal, but not parenteral, immunization with recombinant adenoviral-based vaccine provides potent protection from pulmonary tuberculosis. J Immunol. 2004; 173(10):6357-65. DOI: 10.4049/jimmunol.173.10.6357. View

10.

Kim C, Kunkel E, Boisvert J, Johnston B, Campbell J, Genovese M . Bonzo/CXCR6 expression defines type 1-polarized T-cell subsets with extralymphoid tissue homing potential. J Clin Invest. 2001; 107(5):595-601. PMC: 199429. DOI: 10.1172/JCI11902. View

11.

Liu L, Zhong Q, Tian T, Dubin K, Athale S, Kupper T . Epidermal injury and infection during poxvirus immunization is crucial for the generation of highly protective T cell-mediated immunity. Nat Med. 2010; 16(2):224-7. PMC: 3070948. DOI: 10.1038/nm.2078. View

12.

Pennings J, Kimman T, Janssen R . Identification of a common gene expression response in different lung inflammatory diseases in rodents and macaques. PLoS One. 2008; 3(7):e2596. PMC: 2442866. DOI: 10.1371/journal.pone.0002596. View

13.

Piqueras B, Connolly J, Freitas H, Palucka A, Banchereau J . Upon viral exposure, myeloid and plasmacytoid dendritic cells produce 3 waves of distinct chemokines to recruit immune effectors. Blood. 2005; 107(7):2613-8. PMC: 1895384. DOI: 10.1182/blood-2005-07-2965. View

14.

Griese M . Pulmonary surfactant in health and human lung diseases: state of the art. Eur Respir J. 1999; 13(6):1455-76. DOI: 10.1183/09031936.99.13614779. View

15.

Fulkerson P, Zimmermann N, Hassman L, Finkelman F, Rothenberg M . Pulmonary chemokine expression is coordinately regulated by STAT1, STAT6, and IFN-gamma. J Immunol. 2004; 173(12):7565-74. DOI: 10.4049/jimmunol.173.12.7565. View

16.

Forbes E, Sander C, Ronan E, McShane H, Hill A, Beverley P . Multifunctional, high-level cytokine-producing Th1 cells in the lung, but not spleen, correlate with protection against Mycobacterium tuberculosis aerosol challenge in mice. J Immunol. 2008; 181(7):4955-64. PMC: 2867031. DOI: 10.4049/jimmunol.181.7.4955. View

17.

Liu N, Phillips T, Zhang M, Wang Y, Opferman J, Shah R . Serine protease inhibitor 2A is a protective factor for memory T cell development. Nat Immunol. 2004; 5(9):919-26. DOI: 10.1038/ni1107. View

18.

Liu N, Raja S, Zazzeroni F, Metkar S, Shah R, Zhang M . NF-kappaB protects from the lysosomal pathway of cell death. EMBO J. 2003; 22(19):5313-22. PMC: 204493. DOI: 10.1093/emboj/cdg510. View

19.

Santosuosso M, Zhang X, McCormick S, Wang J, Hitt M, Xing Z . Mechanisms of mucosal and parenteral tuberculosis vaccinations: adenoviral-based mucosal immunization preferentially elicits sustained accumulation of immune protective CD4 and CD8 T cells within the airway lumen. J Immunol. 2005; 174(12):7986-94. DOI: 10.4049/jimmunol.174.12.7986. View

20.

Northfield J, Kasprowicz V, Lucas M, Kersting N, Bengsch B, Bengsh B . CD161 expression on hepatitis C virus-specific CD8+ T cells suggests a distinct pathway of T cell differentiation. Hepatology. 2008; 47(2):396-406. DOI: 10.1002/hep.22040. View