Regulatory T Cells Promote Early Influx of CD8<sup>+</sup>T Cells in the Lungs of Respiratory Syncytial Virus-Infected Mice and Diminish Immunodominance Disparities

Ruckwardt, Tracy J.; Bonaparte, Kathryn L.; Nason, Martha; Graham, Barney S.

doi:10.1128/jvi.00036-09

Cited by 127 publications

(169 citation statements)

References 43 publications

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“…This was accompanied by a delayed exacerbation and a slower recovery. However, no difference in the final viral clearance was seen postinfection as it was achieved completely in both the controls and, albeit slower, in the Treg-depleted mice (34,36,37). Loebbermann et al (38) on the other hand, did describe a decrease in viral load when depleting Treg cells in mice.…”

Section: Treg Cells During Rsv Infectionmentioning

confidence: 93%

“…When the Treg response is inhibited, delayed migration of the CD8 + T-cells out of the peripheral lymph nodes results in delayed viral clearance and increased disease severity (34). In conclusion, Treg cells by no means hinder the viral clearance of RSV and may even facilitate the process (34,36,37).…”

Section: Treg Cells During Rsv Infectionmentioning

confidence: 99%

“…Loebbermann et al (38) on the other hand, did describe a decrease in viral load when depleting Treg cells in mice. These findings can be explained by the fact that during an RSV infection, Treg cells are responsible for early recruitment of activated CD8 + cytotoxic cells out of the draining lymph nodes to the lungs (37). When the Treg response is inhibited, delayed migration of the CD8 + T-cells out of the peripheral lymph nodes results in delayed viral clearance and increased disease severity (34).…”

Section: Treg Cells During Rsv Infectionmentioning

confidence: 99%

“…Although evidence is less conclusive than is the case for the Treg immune response, the Th17 immune response is thought to hamper an efficient viral clearance and further enhance a Th2 immune response resulting in a more severe clinical picture (50). Moreover, the CD8 + T cellular response during RSV infection seems to be counteracted by Th17 cells through IL-17 while being stimulated by Treg cells through promoting early influx of CD8 + T-cells to the lungs, therefore resulting in efficient viral clearance (37,50,55). It is also important to note the opposing effect of IL-10, i.e., inhibitory on Th17 cells and stimulatory on Treg cells (41,74).…”

Section: Th17/treg Balance In Rsv and Its Clinical Relevancementioning

confidence: 99%

“…The Treg and Th17 subsets have distinct and opposing features in this context, as demonstrated by their effects on viral clearance, clinical severity, and Th2-oriented immune response (see Table 1). Specifically, the Treg immune response will ensure an efficient viral clearance and inhibition of the Th2-oriented immune response resulting in a less severe clinical picture (34,(36)(37)(38)(39). Although evidence is less conclusive than is the case for the Treg immune response, the Th17 immune response is thought to hamper an efficient viral clearance and further enhance a Th2 immune response resulting in a more severe clinical picture (50).…”

Section: Th17/treg Balance In Rsv and Its Clinical Relevancementioning

confidence: 99%

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The role of Th17 and Treg responses in the pathogenesis of RSV infection

et al. 2015

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Section: Treg Cells During Rsv Infectionmentioning

confidence: 93%

Section: Treg Cells During Rsv Infectionmentioning

confidence: 99%

Section: Treg Cells During Rsv Infectionmentioning

confidence: 99%

Section: Th17/treg Balance In Rsv and Its Clinical Relevancementioning

confidence: 99%

Section: Th17/treg Balance In Rsv and Its Clinical Relevancementioning

confidence: 99%

See 3 more Smart Citations

The role of Th17 and Treg responses in the pathogenesis of RSV infection

et al. 2015

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From crucial to negligible: Functional CD8⁺T‐cell responses and their dependence on CD4⁺T‐cell help

2012

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CD8 + T cells play an important role in controlling pathogenic infections and are therefore key players in the immune response. It has been shown that among other factors CD4 + T cells can shape the magnitude as well as the quality of primary and/or secondary CD8 + T-cell responses. However, due to the complexity and the differences among diverse immunization or infection models, the overall requirement, the time points, as well as the specific mechanism(s) of CD4 + T-cell help may differ substantially. Here, we summarize current knowledge about the differential requirement of CD4 + T-cell help in promoting primary CD8 + T-cell responses as well as establishing functional memory CD8 + T cells in various experimental settings. Keywords: CD8 + T cells r Differentiation r Memory r T-cell help CD8 + T-cell responsesA number of different parameters influence, by virtue of their strength and composition, CD8 + T-cell activation; they subsequently also shape the size and the phenotypical and functional properties of the resultant memory CD8 + T-cell pool. These parameters include antigen-specific T-cell precursor frequencies [1], the strength of the T-cell receptor interaction with peptide-MHC complexes, and the signals provided by co-stimulatory receptors, as well as innate immune system derived inflammatory cytokines [2,3]. Among the factors that modulate the activation of dendritic cells (DCs), the cells that are the main inducers of CD8 + T-cell responses, is the help provided by CD4 + T cells. CD4 + T-cell engagement of DCs promotes the upregulation of certain costimulatory molecules (such as CD80 and CD86) on, as well as the release of pro-inflammatory cytokines such as IL-12 by, DCs. Thus, in many defined experimental settings, T helper cells have been implicated in the expansion and survival of CD8 + T cells during the primary response, and have a key role in establishing long-lived, functionally robust memory CD8 + T-cell responses [4][5][6][7]. The concept of T-cell help for CD8 + T-cell responses was Correspondence: Prof. Annette Oxenius e-mail: oxenius@micro.biol.ethz.ch further supported by the finding that chemokines secreted by activated CD4 + T helper cells can play a key role in the recruitment of naïve antigen-specific CD8 + T cells to antigen-bearing antigen presenting cells (APCs) in secondary lymphoid organs [8] or to sites of infection [9]. Moreover, in some experimental settings CD4 + T cells were proposed to directly interact with CD8 + T cells, thereby promoting their activation and expansion [10]. Hence, the overall contribution, as well as the mechanism, of helper CD4 + T cells in the initiation of primary and secondary CD8 + T-cell responses is more complex than initially believed and appears to strongly depend on the specific biology of the immunization/infection system.

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Clonotype‐specific avidity influences the dynamics and hierarchy of virus‐specific regulatory and effector CD4⁺T‐cell responses

et al. 2014

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Th17 (IL-17) cells that produce characteristic cytokines [2], T follicular helper (Tfh) cells that promote B cell differentiation[3] and regulatory T (Treg) cells that express transcription factor FoxP3 and regulate effector T-cell responses [4,5]. Interactions of the peptide-MHC (pMHC) complexes with T-cell receptors (TCRs) and subsequent signaling events play an important role in the fate of CD4 + T cells and influence differentiation into functionally distinct CD4 + T-cell subsets [6]. TCR ligation and the presence of particular cytokine environments lead naïve CD4 + T cells to express signature transcription factors and produce hallmark cytokines. In addition, strong signaling mediated by high avidity TCR interactions induces robust proliferation and effectorPublished 2014. This article is a U.S. Government work and is in the public domain in the USA. www.eji-journal.eu Eur. J. Immunol. 2014. 44: 1058-1068 Immunity to infection 1059 cytokine production, while weak signaling mediated by low avidity TCR generally induces limited clonal expansion [7,8]. T cells expressing low avidity TCR have a disadvantage in interclonal competition and restricted access to pathogen epitopes, and thus are less likely to expand into a functionally distinct population when high avidity T clones are present [9,10]. Maintaining a functional Treg-cell population and the balance of effector and regulatory functions is important for recognition and clearance of virus-infected cells with minimal immunopathology and establishment of immunological memory against subsequent infection [11][12][13]. Treg cells have been shown to limit pulmonary inflammation and lung injury induced by pneumocystis infection [14] and to modulate herpes simplex virus-induced inflammatory lesions of the eye [15]. Natural Treg cells reduce the symptoms of West Nile virus infections in both humans and mice, and Treg cell-deficient mice are more likely to develop lethal infection [16]. In addition, Treg cells suppress autoreactive responses and maintain homeostasis of immunocompetent cells to self-antigens [17,18]. Regulatory functions of the Treg cells can also compromise adaptive immune responses and diminish the control of systemic infections [19], delay virus clearance [20], and interfere with immune surveillance of malignant mutations [21]. In RSV-infected mice, Treg cells have been shown to expand during primary infection [22,23] and influence the hierarchy of T-cell responses [22] and immunopathology [24]. The expanded Treg-cell population maintains an environment that can achieve viral clearance while diminishing disease. Depletion of Treg cells enhances virus clearance but also facilitated CD8 + T-cell response-mediated pathogenic inflammation [22,23,25]. Conversely, increasing Treg-cell frequency by administrating IL-2/anti-IL-2 complex reduced lung inflammation without suppressing virus clearance [26]. A diminished Treg-cell response has been observed in response to a secondary exposure to RSV antigens [27]. While the diminished Treg-cell response was ...

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Regulatory T Cells Promote Early Influx of CD8⁺T Cells in the Lungs of Respiratory Syncytial Virus-Infected Mice and Diminish Immunodominance Disparities

Cited by 127 publications

References 43 publications

The role of Th17 and Treg responses in the pathogenesis of RSV infection

The role of Th17 and Treg responses in the pathogenesis of RSV infection

From crucial to negligible: Functional CD8⁺T‐cell responses and their dependence on CD4⁺T‐cell help

Clonotype‐specific avidity influences the dynamics and hierarchy of virus‐specific regulatory and effector CD4⁺T‐cell responses

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Regulatory T Cells Promote Early Influx of CD8+T Cells in the Lungs of Respiratory Syncytial Virus-Infected Mice and Diminish Immunodominance Disparities

Cited by 127 publications

References 43 publications

The role of Th17 and Treg responses in the pathogenesis of RSV infection

The role of Th17 and Treg responses in the pathogenesis of RSV infection

From crucial to negligible: Functional CD8+T‐cell responses and their dependence on CD4+T‐cell help

Clonotype‐specific avidity influences the dynamics and hierarchy of virus‐specific regulatory and effector CD4+T‐cell responses

Contact Info

Product

Resources

About

Regulatory T Cells Promote Early Influx of CD8⁺T Cells in the Lungs of Respiratory Syncytial Virus-Infected Mice and Diminish Immunodominance Disparities

From crucial to negligible: Functional CD8⁺T‐cell responses and their dependence on CD4⁺T‐cell help

Clonotype‐specific avidity influences the dynamics and hierarchy of virus‐specific regulatory and effector CD4⁺T‐cell responses