Primary EBV Infection Induces an Acute Wave of Activated Antigen-Specific Cytotoxic CD4+ T Cells

Meckiff, Benjamin J; Ladell, Kristin; McLaren, James E.; Ryan, Gavin; Leese, Alison M.; James, Eddie A.; Price, David A.; Long, Heather M.

doi:10.4049/jimmunol.1900377

Cited by 41 publications

(39 citation statements)

References 75 publications

(125 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Normally, this mechanism is compensated by the presence of cytotoxic CD4 + Th cells, which keep these types of infections under control (95). Such Th populations have been associated with MS progression (96) and are also formed after EBV infection, producing high levels of IFN-γ, IL-2, granzyme B, and perforin (97,98). Similarly, EBV-and myelin-reactive Th cells from MS patients produce high levels of IFN-γ and IL-2 (6) and strongly respond to memory B cells presenting myelin peptides (99).…”

Section: B Cells As Inducers Of Pathogenic Memory Th Cellsmentioning

confidence: 99%

B and T Cells Driving Multiple Sclerosis: Identity, Mechanisms and Potential Triggers

et al. 2020

View full text Add to dashboard Cite

Historically, multiple sclerosis (MS) has been viewed as being primarily driven by T cells. However, the effective use of anti-CD20 treatment now also reveals an important role for B cells in MS patients. The results from this treatment put forward T-cell activation rather than antibody production by B cells as a driving force behind MS. The main question of how their interaction provokes both B and T cells to infiltrate the CNS and cause local pathology remains to be answered. In this review, we highlight key pathogenic events involving B and T cells that most likely contribute to the pathogenesis of MS. These include (1) peripheral escape of B cells from T cell-mediated control, (2) interaction of pathogenic B and T cells in secondary lymph nodes, and (3) reactivation of B and T cells accumulating in the CNS. We will focus on the functional programs of CNS-infiltrating lymphocyte subsets in MS patients and discuss how these are defined by mechanisms such as antigen presentation, co-stimulation and cytokine production in the periphery. Furthermore, the potential impact of genetic variants and viral triggers on candidate subsets will be debated in the context of MS.

show abstract

Section: B Cells As Inducers Of Pathogenic Memory Th Cellsmentioning

confidence: 99%

B and T Cells Driving Multiple Sclerosis: Identity, Mechanisms and Potential Triggers

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The functional profile of EBV-specific CD4+ T cells is consistent with Th1-like cells: most express T-bet and the predominant cytokine produced in ex vivo stimulation assays is IFNg. Some cells also produce TNFα and/or IL-2, either in combination with IFNg or alone (41, 42). Early observations of raised perforin expression within the total CD4+ T cells of IM patients suggested that cytotoxic CD4+ T cells are present during primary EBV infection (43).…”

Section: The Ebv-specific T-cell Response During Symptomatic Primary mentioning

confidence: 99%

“…Recent ex vivo HLA class II tetramer analysis has now shown that in fact the majority of activated EBV-specific CD4+ T cells express both perforin and granzyme B. Importantly, these cytotoxic proteins were not detected in co-existing influenza A-specific memory CD4+ T cells demonstrating that such expression was not due to non-specific bystander activation (42). Testing with EBV peptides has shown that some EBV-specific CD4+ T cells upregulate cell surface CD107a indicating degranulation and release of perforin and granzyme is possible (41).…”

Section: The Ebv-specific T-cell Response During Symptomatic Primary mentioning

confidence: 99%

The T-cell Response to Epstein-Barr Virus–New Tricks From an Old Dog

2019

Self Cite

View full text Add to dashboard Cite

Epstein-Barr virus (EBV) infects most people and establishes life-long infection controlled by the host's immune system. The genetic stability of the virus, deep understanding of the viral antigens and immune epitopes recognized by the host's T-cell system and the fact that recent infection can be identified by the development of symptomatic infectious mononucleosis makes EBV a powerful system in which to study human immunology. The association between EBV and multiple cancers also means that the lessons learned have strong translational potential. Increasing evidence of a role for resident memory T-cells and non-conventional γδ T-cells in controlling EBV infection suggests new opportunities for research and means the virus will continue to provide exciting new insights into human biology and immunology into the future.

show abstract

“…In contrast, MHC class II restricted CD4 + T cells recognize a broad range of latent EBV antigens, with EBNA1 specific CD4 + T cells present in every healthy virus carrier [49,50]. All latent EBV antigen specific CD8 + and many CD4 + T cells directly recognize LCLs and can kill them, suggesting protective functions against EBV infection and its pathologies in vivo [51][52][53]. Among these T cell responses, EBNA1 and/or LMP1 and LMP2 specific T cells have been selectively isolated or expanded for adoptive transfer into patients with EBV associated malignancies, resulting in clinical benefits [26,[54][55][56].…”

Section: Antigen Specificity Of Protective T Cell Responses Against Ebvmentioning

confidence: 99%

Redirecting T Cells against Epstein–Barr Virus Infection and Associated Oncogenesis

Münz¹

2020

Cells

View full text Add to dashboard Cite

The Epstein–Barr virus (EBV) is associated with lymphomas and carcinomas. For some of these, the adoptive transfer of EBV specific T cells has been therapeutically explored, with clinical success. In order to avoid naturally occurring EBV specific autologous T cell selection from every patient, the transgenic expression of latent and early lytic viral antigen specific T cell receptors (TCRs) to redirect T cells, to target the respective tumors, is being developed. Recent evidence suggests that not only TCRs against transforming latent EBV antigens, but also against early lytic viral gene products, might be protective for the control of EBV infection and associated oncogenesis. At the same time, these approaches might be more selective and cause less collateral damage than targeting general B cell markers with chimeric antigen receptors (CARs). Thus, EBV specific TCR transgenic T cells constitute a promising therapeutic strategy against EBV associated malignancies.

show abstract

Primary EBV Infection Induces an Acute Wave of Activated Antigen-Specific Cytotoxic CD4+ T Cells

Abstract: Key Points Primary EBV infection drives highly cytotoxic virus-specific CD4 + T cell responses. EBV-specific memory CD4 + T cells are polyfunctional but lack cytotoxic activity. Acute EBV-specific CD4-CTLs differ transcriptionally from classical memory CD4-CTLs.

Cited by 41 publications

References 75 publications

B and T Cells Driving Multiple Sclerosis: Identity, Mechanisms and Potential Triggers

B and T Cells Driving Multiple Sclerosis: Identity, Mechanisms and Potential Triggers

The T-cell Response to Epstein-Barr Virus–New Tricks From an Old Dog

Redirecting T Cells against Epstein–Barr Virus Infection and Associated Oncogenesis

Contact Info

Product

Resources

About