B Cell Requirement for Robust Regulatory T Cell Responses to Friend Retrovirus Infection

Moore, Tyler C.; Gonzaga, Lorena M; Mather, Jennifer M.; Messer, Ronald J.; Hasenkrug, Kim J.

doi:10.1128/mbio.01122-17

Cited by 17 publications

(17 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the present experiments do not differentiate between direct Treg-mediated effects on CD8 + T cells and indirect effects mediated through APCs. An obvious experiment would be to test B-cell-deficient or -depleted mice during Treg depletion, but we and others have shown that B cells are required for both homeostatic levels and function of Tregs, as well as Treg responses during FV infection (47–49). Thus, two-way interactions between Tregs and B cells have potent effects on both cell subsets, and testing them independently in vivo is not yet feasible.…”

Section: Resultsmentioning

confidence: 99%

Effects of Friend Virus Infection and Regulatory T Cells on the Antigen Presentation Function of B Cells

Moore

Messer

Gonzaga

et al. 2019

mBio

Self Cite

View full text Add to dashboard Cite

The primary role of B cells in immunity is considered the production of pathogen-specific antibodies, but another, less-well-studied, function of B cells is to present foreign antigens to T cells to stimulate their activation and proliferation. Dendritic cells (DCs) are considered the most important antigen-presenting cells (APCs) for CD8+ T cells, but DCs lose APC function when infected with Friend virus (FV), a model retrovirus of mice. Interestingly, B cells were better able to stimulate CD8+ T cell responses when they were infected with FV. We also found that the activation status of B cells under homeostatic conditions was potently modulated by regulatory T cells. This study illustrates an important link between B cell and T cell responses and illustrates an additional mechanism by which regulatory T cells suppress critical T cell responses during viral infections.

show abstract

Section: Resultsmentioning

confidence: 99%

Effects of Friend Virus Infection and Regulatory T Cells on the Antigen Presentation Function of B Cells

Moore

Messer

Gonzaga

et al. 2019

mBio

Self Cite

View full text Add to dashboard Cite

show abstract

“…This expansion involves Tregs that do not react with FV antigens but rather self-antigens and is fueled by at least two separate mechanisms. First, natural thymus-derived Tregs, which constitutively express the high affinity IL-2 receptor, are polyclonally activated by IL-2 secreted by F-MuLV-reactive CD4+ T cells and by GITR ligand expressed on activated B cells (Myers et al 2013;Moore et al 2017). Second, thymus-derived Tregs bearing Vβ5 family TCRβ chains specifically react with a retroviral superantigen encoded Downloaded from https://academic.oup.com/femsre/article-abstract/43/5/435/5489187 by guest on 09 June 2020 by endogenous mouse mammary tumor virus 9 (MMTV9) (Myers et al 2013;Joedicke et al 2014a).…”

Section: Cd4+ T Cell Responsesmentioning

confidence: 99%

“…Thus, B cells play paradoxically opposing roles during FV infection. They provide proliferative signals to immunsuppressive Tregs, which slows early virus control through suppression of T cell and B cell responses, and they also produce virus-specific antibodies, which are essential for long-term virus control (Moore et al 2017).…”

Section: B Cell Responses and Antibodiesmentioning

confidence: 99%

Friend retrovirus studies reveal complex interactions between intrinsic, innate and adaptive immunity

Dittmer

Sutter

Kassiotis

et al. 2019

FEMS Microbiology Reviews

View full text Add to dashboard Cite

Approximately 4.4% of the human genome is comprised of endogenous retroviral sequences, a record of an evolutionary battle between man and retroviruses. Much of what we know about viral immunity comes from studies using mouse models. Experiments using the Friend virus (FV) model have been particularly informative in defining highly complex anti-retroviral mechanisms of the intrinsic, innate and adaptive arms of immunity. FV studies have unraveled fundamental principles about how the immune system controls both acute and chronic viral infections. They led to a more complete understanding of retroviral immunity that begins with cellular sensing, production of type I interferons, and the induction of intrinsic restriction factors. Novel mechanisms have been revealed, which demonstrate that these earliest responses affect not only virus replication, but also subsequent innate and adaptive immunity. This review on FV immunity not only surveys the complex host responses to a retroviral infection from acute infection to chronicity, but also highlights the many feedback mechanisms that regulate and counter-regulate the various arms of the immune system. In addition, the discovery of molecular mechanisms of immunity in this model have led to therapeutic interventions with implications for HIV cure and vaccine development.

show abstract

“…In FV infections, IL-2 is predominantly produced by FV-specific effector CD4 + helper T cells responding to the infection [ 40 ]. It was recently shown that this IL-2-dependent Treg expansion is also dependent on interactions with B cells [ 48 ]. B cell–dependent Treg signaling occurrs via tumor necrosis factor (TNF) receptor superfamily member 18 (glucocorticoid-induced TNF receptor-related protein [GITR]) ligation with GITR ligand (GITRL) on B cells [ 48 ].…”

Section: Mechanisms Of Treg Expansion And/or Accrual During Retroviramentioning

confidence: 99%

“…It was recently shown that this IL-2-dependent Treg expansion is also dependent on interactions with B cells [ 48 ]. B cell–dependent Treg signaling occurrs via tumor necrosis factor (TNF) receptor superfamily member 18 (glucocorticoid-induced TNF receptor-related protein [GITR]) ligation with GITR ligand (GITRL) on B cells [ 48 ]. Of note, GITR–GITRL interactions are also required to control autoimmunity through regulation of Treg homeostasis [ 49 ].…”

Section: Mechanisms Of Treg Expansion And/or Accrual During Retroviramentioning

confidence: 99%

Regulatory T cells in retroviral infections

Hasenkrug¹,

Chougnet

Dittmer

2018

PLoS Pathog

Self Cite

View full text Add to dashboard Cite

Tight regulation of immune responses is not only critical for preventing autoimmune diseases but also for preventing immunopathological damage during infections in which overactive immune responses may be more harmful for the host than the pathogen itself. Regulatory T cells (Tregs) play a critical role in this regulation, which was discovered using the Friend retrovirus (FV) mouse model. Subsequent FV studies revealed basic biological information about Tregs, including their suppressive activity on effector cells as well as the molecular mechanisms of virus-induced Treg expansion. Treg suppression not only limits immunopathology but also prevents complete elimination of pathogens contributing to chronic infections. Therefore, Tregs play a complex role in the pathogenesis of persistent retroviral infections. New therapeutic concepts to reactivate effector T-cell responses in chronic viral infections by manipulating Tregs also came from work with the FV model. This knowledge initiated many studies to characterize the role of Tregs in HIV pathogenesis in humans, where a complex picture is emerging. On one hand, Tregs suppress HIV-specific effector T-cell responses and are themselves targets of infection, but on the other hand, Tregs suppress HIV-induced immune hyperactivation and thus slow the infection of conventional CD4+ T cells and limit immunopathology. In this review, the basic findings from the FV mouse model are put into perspective with clinical and basic research from HIV studies. In addition, the few Treg studies performed in the simian immunodeficiency virus (SIV) monkey model will also be discussed. The review provides a comprehensive picture of the diverse role of Tregs in different retroviral infections and possible therapeutic approaches to treat retroviral chronicity and pathogenesis by manipulating Treg responses.

show abstract

B Cell Requirement for Robust Regulatory T Cell Responses to Friend Retrovirus Infection

Cited by 17 publications

References 72 publications

Effects of Friend Virus Infection and Regulatory T Cells on the Antigen Presentation Function of B Cells

Effects of Friend Virus Infection and Regulatory T Cells on the Antigen Presentation Function of B Cells

Friend retrovirus studies reveal complex interactions between intrinsic, innate and adaptive immunity

Regulatory T cells in retroviral infections

Contact Info

Product

Resources

About