Absence of Cross-presenting Cells in the Salivary Gland and Viral Immune Evasion Confine Cytomegalovirus Immune Control to Effector CD4 T Cells

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2011 Sep 9

PMID 21901102

Citations 60

Authors

Senta M Walton

Sanja Mandaric

Nicole Torti

Albert Zimmermann

Hartmut Hengel

Annette Oxenius

Affiliations

Soon will be listed here.

Abstract

Horizontal transmission of cytomegaloviruses (CMV) occurs via prolonged excretion from mucosal surfaces. We used murine CMV (MCMV) infection to investigate the mechanisms of immune control in secretory organs. CD4 T cells were crucial to cease MCMV replication in the salivary gland (SG) via direct secretion of IFNγ that initiated antiviral signaling on non-hematopoietic cells. In contrast, CD4 T cell helper functions for CD8 T cells or B cells were dispensable. Despite SG-resident MCMV-specific CD8 T cells being able to produce IFNγ, the absence of MHC class I molecules on infected acinar glandular epithelial cells due to viral immune evasion, and the paucity of cross-presenting antigen presenting cells (APCs) prevented their local activation. Thus, local activation of MCMV-specific T cells is confined to the CD4 subset due to exclusive presentation of MCMV-derived antigens by MHC class II molecules on bystander APCs, resulting in IFNγ secretion interfering with viral replication in cells of non-hematopoietic origin.

Citing Articles

CD4+ but not CD8+ T cells are required for protection against severe guinea pig cytomegalovirus infections.

Rollman T, Berkebile Z, Hicks D, Hatfield J, Chauhan P, Pravetoni M PLoS Pathog. 2024; 20(11):e1012515.

PMID: 39495799 PMC: 11563410. DOI: 10.1371/journal.ppat.1012515.

The Multifaceted Roles of NK Cells in the Context of Murine Cytomegalovirus and Lymphocytic Choriomeningitis Virus Infections.

Hamdan T Immune Netw. 2024; 24(4):e29.

PMID: 39246620 PMC: 11377952. DOI: 10.4110/in.2024.24.e29.

Spatial kinetics and immune control of murine cytomegalovirus infection in the salivary glands.

Byrne C, Marquez A, Cai B, Coombs D, Gantt S PLoS Comput Biol. 2024; 20(8):e1011940.

PMID: 39150988 PMC: 11357091. DOI: 10.1371/journal.pcbi.1011940.

Immune surveillance of cytomegalovirus in tissues.

Mihalic A, Zeleznjak J, Lisnic B, Jonjic S, Juranic Lisnic V, Brizic I Cell Mol Immunol. 2024; 21(9):959-981.

PMID: 39134803 PMC: 11364667. DOI: 10.1038/s41423-024-01186-2.

IL-27 expression regulation and its effects on adaptive immunity against viruses.

Andres-Martin F, James C, Catalfamo M Front Immunol. 2024; 15:1395921.

PMID: 38966644 PMC: 11222398. DOI: 10.3389/fimmu.2024.1395921.

References

Del Rio M, Bernhardt G, Rodriguez-Barbosa J, Forster R . Development and functional specialization of CD103+ dendritic cells. Immunol Rev. 2010; 234(1):268-81. DOI: 10.1111/j.0105-2896.2009.00874.x. View

Munks M, Pinto A, Doom C, Hill A . Viral interference with antigen presentation does not alter acute or chronic CD8 T cell immunodominance in murine cytomegalovirus infection. J Immunol. 2007; 178(11):7235-41. DOI: 10.4049/jimmunol.178.11.7235. View

Klenovsek K, Weisel F, Schneider A, Appelt U, Jonjic S, Messerle M . Protection from CMV infection in immunodeficient hosts by adoptive transfer of memory B cells. Blood. 2007; 110(9):3472-9. DOI: 10.1182/blood-2007-06-095414. View

Rahemtulla A, Schilham M, Kundig T, Sambhara S, Narendran A, Arabian A . Normal development and function of CD8+ cells but markedly decreased helper cell activity in mice lacking CD4. Nature. 1991; 353(6340):180-4. DOI: 10.1038/353180a0. View

Ruedl C, Storni T, Lechner F, Bachi T, Bachmann M . Cross-presentation of virus-like particles by skin-derived CD8(-) dendritic cells: a dispensable role for TAP. Eur J Immunol. 2002; 32(3):818-25. DOI: 10.1002/1521-4141(200203)32:3<818::AID-IMMU818>3.0.CO;2-U. View

Jonjic S, Pavic I, Lucin P, Rukavina D, Koszinowski U . Efficacious control of cytomegalovirus infection after long-term depletion of CD8+ T lymphocytes. J Virol. 1990; 64(11):5457-64. PMC: 248597. DOI: 10.1128/JVI.64.11.5457-5464.1990. View

Pearce E, Shedlock D, Shen H . Functional characterization of MHC class II-restricted CD8+CD4- and CD8-CD4- T cell responses to infection in CD4-/- mice. J Immunol. 2004; 173(4):2494-9. DOI: 10.4049/jimmunol.173.4.2494. View

Walton S, Wyrsch P, Munks M, Zimmermann A, Hengel H, Hill A . The dynamics of mouse cytomegalovirus-specific CD4 T cell responses during acute and latent infection. J Immunol. 2008; 181(2):1128-34. DOI: 10.4049/jimmunol.181.2.1128. View

Tessmer M, Reilly E, Brossay L . Salivary gland NK cells are phenotypically and functionally unique. PLoS Pathog. 2011; 7(1):e1001254. PMC: 3020929. DOI: 10.1371/journal.ppat.1001254. View

10.

Scalzo A, Manzur M, Forbes C, Brown M, Shellam G . NK gene complex haplotype variability and host resistance alleles to murine cytomegalovirus in wild mouse populations. Immunol Cell Biol. 2005; 83(2):144-9. DOI: 10.1111/j.1440-1711.2005.01311.x. View

11.

Jonjic S, Mutter W, Weiland F, Reddehase M, Koszinowski U . Site-restricted persistent cytomegalovirus infection after selective long-term depletion of CD4+ T lymphocytes. J Exp Med. 1989; 169(4):1199-212. PMC: 2189231. DOI: 10.1084/jem.169.4.1199. View

12.

Kontgen F, Suss G, Stewart C, Steinmetz M, Bluethmann H . Targeted disruption of the MHC class II Aa gene in C57BL/6 mice. Int Immunol. 1993; 5(8):957-64. DOI: 10.1093/intimm/5.8.957. View

13.

Altman J, Moss P, Goulder P, Barouch D, McHeyzer-Williams M, Bell J . Phenotypic analysis of antigen-specific T lymphocytes. Science. 1996; 274(5284):94-6. DOI: 10.1126/science.274.5284.94. View

14.

Tyznik A, Sun J, Bevan M . The CD8 population in CD4-deficient mice is heavily contaminated with MHC class II-restricted T cells. J Exp Med. 2004; 199(4):559-65. PMC: 2211827. DOI: 10.1084/jem.20031961. View

15.

Walton S, Torti N, Mandaric S, Oxenius A . T-cell help permits memory CD8(+) T-cell inflation during cytomegalovirus latency. Eur J Immunol. 2011; 41(8):2248-59. DOI: 10.1002/eji.201141575. View

16.

Arens R, Wang P, Sidney J, Loewendorf A, Sette A, Schoenberger S . Cutting edge: murine cytomegalovirus induces a polyfunctional CD4 T cell response. J Immunol. 2008; 180(10):6472-6. PMC: 2587066. DOI: 10.4049/jimmunol.180.10.6472. View

17.

Snyder C, Loewendorf A, Bonnett E, Croft M, Benedict C, Hill A . CD4+ T cell help has an epitope-dependent impact on CD8+ T cell memory inflation during murine cytomegalovirus infection. J Immunol. 2009; 183(6):3932-41. PMC: 2766182. DOI: 10.4049/jimmunol.0900227. View

18.

Gu H, Zou Y, Rajewsky K . Independent control of immunoglobulin switch recombination at individual switch regions evidenced through Cre-loxP-mediated gene targeting. Cell. 1993; 73(6):1155-64. DOI: 10.1016/0092-8674(93)90644-6. View

19.

Doom C, Hill A . MHC class I immune evasion in MCMV infection. Med Microbiol Immunol. 2008; 197(2):191-204. DOI: 10.1007/s00430-008-0089-y. View

20.

Campbell A, Cavanaugh V, Slater J . The salivary glands as a privileged site of cytomegalovirus immune evasion and persistence. Med Microbiol Immunol. 2008; 197(2):205-13. DOI: 10.1007/s00430-008-0077-2. View