The Role of T-Cell-Mediated Mechanisms in Virus Infections of the Nervous System

Dörries, Rüdiger

doi:10.1007/978-3-662-10356-2_11

Cited by 54 publications

(70 citation statements)

References 104 publications

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“…It is likely that activation allows lymphocytes to follow chemokine gradients within the brain, but recognition of specific antigen is essential for functionality. Rapid and specific immune responses help limit the degree of viral dissemination and thereby minimize secondary damage to healthy cells (10) and may reduce the magnitude of subsequent viral latency (50). This can be supported by our observation of a drastically reduced incidence of residual DNA levels in the brain from SCID mice given MCMV-immune versus naïve lymphocytes following systemic MCMV challenge.…”

Section: Discussionsupporting

confidence: 56%

“…One possible mechanism for viral clearance in the brain is through interaction of activated T cells with adjacent microglia or astrocytes functioning as antigen-presenting cells. Both cell types are capable of presenting epitopes though class II MHC presentation to CD4 ϩ T cells (10,12,17,45). Additionally, NK cells secrete IFN-␥ following CNS infection, which may divert the immune response to a Th1-type CD4 ϩ T-dominated response.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, NK cells secrete IFN-␥ following CNS infection, which may divert the immune response to a Th1-type CD4 ϩ T-dominated response. Infiltrating T cells may then upregulate antigen-presenting cell MHC expression, further stimulating virus elimination (10).…”

Section: Discussionmentioning

confidence: 99%

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CD4⁺T-Cell Reconstitution Reduces Cytomegalovirus in the Immunocompromised Brain

Reuter¹,

Wilson²,

Idoko³

et al. 2005

J Virol

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Cytomegalovirus (CMV) infection is the most common opportunistic infection of the central nervous systemin patients with human immunodeficiency virus or AIDS or on immunosuppressive drug therapy. Despite medical management, infection may be refractory to treatment and continues to cause significant morbidity and mortality. We investigated adoptive transfer as an approach to treat and prevent neurotropic CMV infection in an adult immunodeficient mouse model. SCID mice were challenged with intracranial murine CMV (MCMV) and reconstituted with MCMV-or vesicular stomatitis virus (VSV)-sensitized splenocytes, T cells, or T-cell subsets. T cells labeled with vital dye or that constitutively generated green fluorescent protein (GFP) were identified in the brain as early as 3 days following peripheral transfer. Regardless of specificity, activated T cells localized to regions of the brain containing CMV, however, only those specific for CMV were effective at clearing virus. Reconstitution with unsorted MCMV-immune splenocytes, enriched T-cell fractions, or CD4؉ cells significantly reduced virus levels in the brain within 7 days and also prevented clinical disease, in significant contrast with mice given VSV-immune unsorted splenocytes, MCMV-immune CD8 ؉ T cells, and SCID control mice. Results suggest CMV-immune T cells (particularly CD4 ؉ ) rapidly cross the blood-brain barrier, congregate at sites of specific CMV infection, and functionally eliminate acute CMV within the brain. In addition, when CMV-immune splenocytes were administered prior to a peripheral CMV challenge, CMV entry into the immunocompromised brain was prevented. Systemic adoptive transfer may be a rapid and effective approach to preventing CMV entrance into the brain and for reducing neurotropic infection.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

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CD4⁺T-Cell Reconstitution Reduces Cytomegalovirus in the Immunocompromised Brain

Reuter¹,

Wilson²,

Idoko³

et al. 2005

J Virol

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“…Subsequently, these APC's can stimulate CD41 T-cells that are reactive to the original tumor antigen or to newer antigens, phenomenon called epitope spreading. 31,32 These CD41 cells are required for the maintenance of CD81 T-cell numbers and CTL function. Previously, in the absence of CD41 T cells, CD81 T cells were not found within the tumor mass.…”

Section: Discussionmentioning

confidence: 99%

Circulating human papillomavirus type 16 specific T‐cells are associated with HLA Class I expression on tumor cells, but not related to the amount of viral oncogene transcripts

Boer¹,

Jordanova²,

Poelgeest³

et al. 2007

Intl Journal of Cancer

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Human papillomavirus (HPV) is a necessary factor in the pathogenesis of cervical cancer. Circulating HPV-specific T-cells responding to the E6 and E7 HPV proteins can be detected only in half of cervical cancer patients. Potential explanations for the absence of this response are lack of sufficient amounts of antigen to activate the immune response or local immune escape mechanisms. We studied the relationship between HPV 16 E6/E7 oncogene mRNA expression, human leukocyte antigen (HLA) expression on tumor cells and the presence of circulating E6-and E7-specific T-cell responses in cervical cancer patients. The amount of antigen was assessed by HPV E6/E7 mRNA expression levels measured by quantitative polymerase chain reaction. HLA Class I and Class II expression on tumor cells was analyzed by immunohistochemistry. A proliferative HPV-specific T-cell response was detected in 15/29 patients. The amount of HPV E6/E7 mRNA was not related to the presence of immune response. HLA Class I expression was downregulated in 19 patients and completely lost in 7 patients. HLA Class II expression was upregulated in 18 patients. HLA Class I expression on tumor cells showed a strong correlation with immunity (p 5 0.001). Explicitly, all patients with complete HLA loss lacked HPV specific T-cell responses. The presence of circulating HPV-specific T-cells might reflect ongoing antitumor response that is sustained by CD81 T-cells killing HLA Class I positive cancer cells. We hypothesize that HLA Class I expression status on tumor cells might as well influence the response to HPV E6/E7 directed immunotherapy. ' 2007 Wiley-Liss, Inc.Key words: human papillomavirus; cervical cancer; HLA; T-cell response; mRNA expression Cervical cancer is the second most common cancer in women worldwide, with 400,000 new cases diagnosed each year. Infection with human papillomavirus (HPV) is a necessary cause of cervical cancer, as it is detected in 99.7% of cases. 1 HPV Type 16 is the most prevalent type, accounting for 50% of all cervical cancers. 2 The 2 viral oncoproteins, E6 and E7 are constitutively expressed and inactivate the tumor suppressor proteins p53 and pRb, respectively, causing deregulation of the cell cycle. 3 The E6 and E7 proteins are transcribed from 1 shared transcript. In addition to the full-length E6/E7 mRNA, HPV 16 generates 2 spliced transcripts, referred to as E6*I and E6*II. The function of the spliced transcripts is not well understood. 4,5 Therapeutic vaccinations aim at generating specific T-cell responses to these oncogenes. 6 The cellular immune response is likely to be an important mechanism for the clearance of established HPV infections. It has been shown that immunosuppressed individuals are more likely to have persistent HPV infections, whereas a T-cell response can usually be detected in healthy individuals. 6,7 In a minority of patients with high grade Cervical Intraepithelial Neoplasia (CIN) as well as in half of the cervical cancer patients a specific T-cell response to E6 and E7 can be detected. [8][9][10] Ce...

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“…For instance, some latent viruses such as JC virus or varicella zoster produce clinical syndromes mainly in immuno-compromised individuals. MHC and co-stimulatory molecules are strongly increased in CNS infection and a number of CNS pathologic conditions, including ischemia, neoplasm, traumatic nerve injury and neurodegenerative diseases such as AD, PD, MS, HIV-dementia and Creutzfeldt-Jacob disease (Maehlen et al, 1989;McGeer et al, 1993;Graeber et al, 1998;Perry, 1998;Dorries, 2001;Piehl and Lidman, 2001;O'Keefe et al, 2002;Owens, 2002). Recent evidence has implied that the CNS equips itself with a unique defense system with its own molecular and cellular components despite sharing certain properties with the peripheral immune system.…”

Section: Unique Immune Properties Of the Central Nervous Systemmentioning

confidence: 99%

Microglia, major player in the brain inflammation: their roles in the pathogenesis of Parkinson's disease

Kim

Joh²

2006

Exp Mol Med

581

450

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Inflammation, a self-defensive reaction against various pathogenic stimuli, may become harmful self-damaging process. Increasing evidence has linked chronic inflammation to a number of neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis. In the central nervous system, microglia, the resident innate immune cells play major role in the inflammatory process. Although they form the first line of defense for the neural parenchyma, uncontrolled activation of microglia may directly toxic to neurons by releasing various substances such as inflammatory cytokines (IL-1β, TNF-α, IL-6), NO, PGE2, and superoxide. Moreover, our recent study demonstrated that activated microglia phagocytose not only damaged cell debris but also neighboring intact cells. It further supports their active participation in self-perpetuating neuronal damaging cycles. In the following review, we discuss microglial responses to damaging neurons, known activators released from injured neurons and how microglia cause neuronal degeneration. In the last part, microglial activation and their role in PD are discussed in depth.

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The Role of T-Cell-Mediated Mechanisms in Virus Infections of the Nervous System

Cited by 54 publications

References 104 publications

CD4⁺T-Cell Reconstitution Reduces Cytomegalovirus in the Immunocompromised Brain

CD4⁺T-Cell Reconstitution Reduces Cytomegalovirus in the Immunocompromised Brain

Circulating human papillomavirus type 16 specific T‐cells are associated with HLA Class I expression on tumor cells, but not related to the amount of viral oncogene transcripts

Microglia, major player in the brain inflammation: their roles in the pathogenesis of Parkinson's disease

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The Role of T-Cell-Mediated Mechanisms in Virus Infections of the Nervous System

Cited by 54 publications

References 104 publications

CD4+T-Cell Reconstitution Reduces Cytomegalovirus in the Immunocompromised Brain

CD4+T-Cell Reconstitution Reduces Cytomegalovirus in the Immunocompromised Brain

Circulating human papillomavirus type 16 specific T‐cells are associated with HLA Class I expression on tumor cells, but not related to the amount of viral oncogene transcripts

Microglia, major player in the brain inflammation: their roles in the pathogenesis of Parkinson's disease

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Product

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CD4⁺T-Cell Reconstitution Reduces Cytomegalovirus in the Immunocompromised Brain

CD4⁺T-Cell Reconstitution Reduces Cytomegalovirus in the Immunocompromised Brain