Inverted immunodominance and impaired cytolytic function of CD8+ T cells during viral persistence in the central nervous system - PubMed (original) (raw)
. 1999 Sep 15;163(6):3379-87.
Affiliations
- PMID: 10477608
Inverted immunodominance and impaired cytolytic function of CD8+ T cells during viral persistence in the central nervous system
C C Bergmann et al. J Immunol. 1999.
Abstract
Mice infected with the neurotropic JHM strain of mouse hepatitis virus (JHMV) clear infectious virus; nevertheless, virus persists in the CNS as noninfectious RNA, resulting in ongoing primary demyelination. Phenotypic and functional analysis of CNS infiltrating cells during acute infection revealed a potent regional CD8+ T cell response comprising up to 50% virus-specific T cells. The high prevalence of virus-specific T cells correlated with ex vivo cytolytic activity and efficient reduction in viral titers. Progressive viral clearance coincided with the loss of cytolytic activity, but retention of IFN-gamma secretion and increased expression of the early activation marker CD69, indicating differential regulation of effector function. Although the total number of infiltrating T cells declined following clearance of infectious virus, CD8+ T cells, both specific for the dominant viral epitopes and of unknown specificity, were retained within the CNS, suggesting an ongoing T cell response during persistent CNS infection involving a virus-independent component. Reversed immunodominance within the virus-specific CD8+ T cell population further indicated epitope-specific regulation, supporting ongoing T cell activation. Even in the absence of infectious virus, the CNS thus provides an environment that maintains both unspecific and Ag-specific CD8+ T cells with restricted effector function. Chronic T cell stimulation may thus play a role in preventing viral recrudescence, while increasing the risk of pathological conditions, such as demyelination.
Similar articles
- Selection of CD8+ T cells with highly focused specificity during viral persistence in the central nervous system.
Marten NW, Stohlman SA, Smith-Begolka W, Miller SD, Dimacali E, Yao Q, Stohl S, Goverman J, Bergmann CC. Marten NW, et al. J Immunol. 1999 Apr 1;162(7):3905-14. J Immunol. 1999. PMID: 10201909 - IFN-gamma is required for viral clearance from central nervous system oligodendroglia.
Parra B, Hinton DR, Marten NW, Bergmann CC, Lin MT, Yang CS, Stohlman SA. Parra B, et al. J Immunol. 1999 Feb 1;162(3):1641-7. J Immunol. 1999. PMID: 9973424 - The art of survival during viral persistence.
Stohlman SA, Ramakrishna C, Tschen SI, Hinton DR, Bergmann CC. Stohlman SA, et al. J Neurovirol. 2002 Dec;8 Suppl 2:53-8. doi: 10.1080/13550280290167884. J Neurovirol. 2002. PMID: 12491152 - MHV infection of the CNS: mechanisms of immune-mediated control.
Marten NW, Stohlman SA, Bergmann CC. Marten NW, et al. Viral Immunol. 2001;14(1):1-18. doi: 10.1089/08828240151061329. Viral Immunol. 2001. PMID: 11270593 Review. - Pathogenesis of acute and chronic central nervous system infection with variants of mouse hepatitis virus, strain JHM.
Templeton SP, Perlman S. Templeton SP, et al. Immunol Res. 2007;39(1-3):160-72. doi: 10.1007/s12026-007-0079-y. Immunol Res. 2007. PMID: 17917063 Free PMC article. Review.
Cited by
- Advances in viral encephalitis: Viral transmission, host immunity, and experimental animal models.
Yang D, Li XJ, Tu DZ, Li XL, Wei B. Yang D, et al. Zool Res. 2023 May 18;44(3):525-542. doi: 10.24272/j.issn.2095-8137.2023.025. Zool Res. 2023. PMID: 37073800 Free PMC article. Review. - Trem2 deficiency impairs recovery and phagocytosis and dysregulates myeloid gene expression during virus-induced demyelination.
Hwang M, Savarin C, Kim J, Powers J, Towne N, Oh H, Bergmann CC. Hwang M, et al. J Neuroinflammation. 2022 Nov 4;19(1):267. doi: 10.1186/s12974-022-02629-1. J Neuroinflammation. 2022. PMID: 36333761 Free PMC article. - Hepatitis B virus polymerase-specific T cell epitopes shift in a mouse model of chronic infection.
Hasanpourghadi M, Novikov M, Newman D, Xiang Z, Zhou XY, Magowan C, Ertl HCJ. Hasanpourghadi M, et al. Virol J. 2021 Dec 7;18(1):242. doi: 10.1186/s12985-021-01712-y. Virol J. 2021. PMID: 34876153 Free PMC article. - Dissociation of neonatal and adult mice brain for simultaneous analysis of microglia, astrocytes and infiltrating lymphocytes by flow cytometry.
Calvo B, Rubio F, Fernández M, Tranque P. Calvo B, et al. IBRO Rep. 2020 Jan 13;8:36-47. doi: 10.1016/j.ibror.2019.12.004. eCollection 2020 Jun. IBRO Rep. 2020. PMID: 32215337 Free PMC article. - Dynamics of Virus-Specific Memory B Cells and Plasmablasts following Viral Infection of the Central Nervous System.
Atkinson JR, Hwang M, Reyes-Rodriguez A, Bergmann CC. Atkinson JR, et al. J Virol. 2019 Jan 4;93(2):e00875-18. doi: 10.1128/JVI.00875-18. Print 2019 Jan 15. J Virol. 2019. PMID: 30333176 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Molecular Biology Databases
Research Materials