IL-15 trans-presentation by pulmonary dendritic cells promotes effector CD8 T cell survival during influenza virus infection

McGill, Jodi L.; Rooijen, Nico van; Legge, Kevin L.

doi:10.1084/jem.20091711

Cited by 124 publications

(153 citation statements)

References 53 publications

(94 reference statements)

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“…Our preliminary data shows that CD28 signaling is also required for higher expression of CD122 (data not shown), and we believe that increased expression of this receptor subunit on CD8 + T cells may be important for both IL-2 and IL-15 signaling. Others have shown that DCs may also provide prosurvival signals to virus-specific CD8 + T cells via trans-presentation of IL-15 (46). However, our studies indicate that IL-15 alone may not be sufficient for survival, as the virus-specific effector CD8 + T cells transferred into CD80 2/2 CD86 2/2 -deficient animals did not expand optimally.…”

Section: Discussioncontrasting

confidence: 68%

Dendritic Cells and CD28 Costimulation Are Required To Sustain Virus-Specific CD8+ T Cell Responses during the Effector Phase In Vivo

Dolfi

Duttagupta

Boesteanu

et al. 2011

The Journal of Immunology

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Although much is known about the initiation of immune responses, much less is known about what controls the effector phase. CD8+ T cell responses are believed to be programmed in lymph nodes during priming without any further contribution by dendritic cells (DCs) and Ag. In this study, we report the requirement for DCs, Ag, and CD28 costimulation during the effector phase of the CD8+ T cell response. Depleting DCs or blocking CD28 after day 6 of primary influenza A virus infection decreases the virus-specific CD8+ T cell response by inducing apoptosis, and this results in decreased viral clearance. Furthermore, effector CD8+ T cells adoptively transferred during the effector phase fail to expand without DC, CD28 costimulation, and cognate Ag. The absence of costimulation also leads to reduced survival of virus-specific effector cells as they undergo apoptosis mediated by the proapoptotic molecule Bim. Finally, IL-2 treatment restored the effector response in the absence of CD28 costimulation. Thus, in contrast to naive CD8+ T cells, which undergo an initial Ag-independent proliferation, effector CD8+ T cells expanding in the lungs during the effector phase require Ag, CD28 costimulation, and DCs for survival and expansion. These requirements would greatly impair effector responses against viruses and tumors that are known to inhibit DC maturation and in chronic infections and aging where CD28−/− CD8+ T cells accumulate.

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Section: Discussioncontrasting

confidence: 68%

Dendritic Cells and CD28 Costimulation Are Required To Sustain Virus-Specific CD8+ T Cell Responses during the Effector Phase In Vivo

Dolfi

Duttagupta

Boesteanu

et al. 2011

The Journal of Immunology

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“…Reports of recent studies in viral infection models indicate that Ag-experienced T cells require cognate interactions with tissue DCs for local expansion and acquisition of effector functions (8,9,46). The concept that tumor stromal cells participate in crosspresentation of tumor-derived Ags and serve as targets for immune destruction by CTLs is well supported by previous studies (45,47,48); however, the identity of the APCs in these studies was not defined.…”

Section: Discussionmentioning

confidence: 98%

Tumors Suppress In Situ Proliferation of Cytotoxic T Cells by Promoting Differentiation of Gr-1+ Conventional Dendritic Cells through IL-6

Diao

Zhao

Winter

et al. 2011

The Journal of Immunology

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Cancers are often accompanied by inflammation, which can promote tumor growth, invasion, and metastases. We show that the tumor microenvironment induces the development of a Gr-1+ conventional dendritic cell (cDC) subpopulation that is functionally defective. Gr-1+cDCs differentiated from recruited immediate precursors of cDCs, a process supported by the inflammatory cytokine milieu in tumors. Inhibition of Gr-1+cDC differentiation enhanced intratumor expansion of cytotoxic CD8+ T cells (CTLs), resulting in suppression of tumor growth. Diphtheria toxin treatment of CD11c–diphtheria toxin receptor chimeras revealed the importance of intratumor cDCs in stimulating CTL proliferation in situ. Our study demonstrates a key role of intratumor cDCs in determining antitumor CTL responses and suggests that they may be an appropriate target for tumor immunotherapy.

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“…Furthermore, the IFN I-induced proliferation was shown to be independent of TCR interaction with MHC class I [14] and may be facilitated by interleukin (IL)-15 production by antigenpresenting cells [16]. Resting CD44 high CD8…”

Section: Introductionmentioning

confidence: 99%

Influenza infection results in local expansion of memory CD8+ T cells with antigen non-specific phenotype and function

Sckisel

Tietze

Zamora

et al. 2013

Clinical and Experimental Immunology

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Summary Primary viral infections induce activation of CD8+ T cells responsible for effective resistance. We sought to characterize the nature of the CD8 + T cell expansion observed after primary viral infection with influenza. Infection of naive mice with different strains of influenza resulted in the rapid expansion of memory CD8 + T cells exhibiting a unique bystander phenotype with significant up-regulation of natural killer group 2D (NKG2D), but not CD25, on the CD44 high CD8+ T cells, suggesting an antigen non-specific phenotype. We further confirmed the non-specificity of this phenotype on ovalbuminspecific (OT-I) CD8 + T cells, which are not specific to influenza. These nonspecific CD8 + T cells also displayed increased lytic capabilities and were observed primarily in the lung. Thus, influenza infection was shown to induce a rapid, antigen non-specific memory T cell expansion which is restricted to the specific site of inflammation. In contrast, CD8 + T cells of a similar phenotype could be observed in other organs following administration of systemic agonistic anti-CD40 and interleukin-2 immunotherapy, demonstrating that bystander expansion in multiple sites is possible depending on whether the nature of activation is either acute or systemic. Finally, intranasal blockade of NKG2D resulted in a significant increase in viral replication early during the course of infection, suggesting that NKG2D is a critical mediator of anti-influenza responses prior to the initiation of adaptive immunity. These results characterize further the local bystander expansion of tissue-resident, memory CD8 + T cells which, due to their early induction, may play an important NKG2D-mediated, antigen non-specific role during the early stages of viral infection.

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IL-15 trans-presentation by pulmonary dendritic cells promotes effector CD8 T cell survival during influenza virus infection

Cited by 124 publications

References 53 publications

Dendritic Cells and CD28 Costimulation Are Required To Sustain Virus-Specific CD8+ T Cell Responses during the Effector Phase In Vivo

Dendritic Cells and CD28 Costimulation Are Required To Sustain Virus-Specific CD8+ T Cell Responses during the Effector Phase In Vivo

Tumors Suppress In Situ Proliferation of Cytotoxic T Cells by Promoting Differentiation of Gr-1+ Conventional Dendritic Cells through IL-6

Influenza infection results in local expansion of memory CD8+ T cells with antigen non-specific phenotype and function

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