An alternative signal 3: CD8+ T cell memory independent of IL-12 and type I IFN is dependent on CD27/OX40 signaling

Sanchez, Phillip J.; Kedl, Ross M.

doi:10.1016/j.vaccine.2011.12.017

Cited by 26 publications

(24 citation statements)

References 46 publications

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“…(combined TLR/CD40 vaccination) (23,24). In contrast to other forms of vaccination/immunization, T-cell intrinsic stimulation from classical Signal 3 cytokines such as type I IFN or IL-12 were not required for T-cell expansion, polarization, or memory generation (25,26). Literature searches for other cytokines capable of dramatically influencing T-cell polarization/differentiation drew attention to the IL-12 family member IL-27 (11,27,28).…”

Section: Resultsmentioning

confidence: 99%

IL-27 is required for shaping the magnitude, affinity distribution, and memory of T cells responding to subunit immunization

Pennock

Gapin

Kedl

2014

Proc. Natl. Acad. Sci. U.S.A.

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An elusive goal of cellular immune vaccines is the generation of large numbers of antigen-specific T cells in response to subunit immunization. A broad spectrum of cytokines and cell-surface costimulatory molecules are known to shape the programming, magnitude, and repertoire of T cells responding to vaccination. We show here that the majority of innate immune receptor agonistbased vaccine adjuvants unexpectedly depend on IL-27 for eliciting CD4 + and CD8 + T-cell responses. This is in sharp contrast to infectious challenge, which generates T-cell responses that are IL-27-independent. Mixed bone marrow chimera experiments demonstrate that IL-27 dependency is T cell-intrinsic, requiring T-cell expression of IL-27Rα. Further, we show that IL-27 dependency not only dictates the magnitude of vaccine-elicited T-cell responses but also is critical for the programming and persistence of high-affinity T cells to subunit immunization. Collectively, our data highlight the unexpected central importance of IL-27 in the generation of robust, high-affinity cellular immune responses to subunit immunization.

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Section: Resultsmentioning

confidence: 99%

IL-27 is required for shaping the magnitude, affinity distribution, and memory of T cells responding to subunit immunization

Pennock

Gapin

Kedl

2014

Proc. Natl. Acad. Sci. U.S.A.

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“…The lower CD8 ϩ T cell response observed in WT mice relies on type I IFN-induced downregulation of CD8 ϩ T cell priming and induction of CD4 ϩ T regulatory cells that secrete IL-10 (64). In the absence of type I IFN signaling, other signals, such as IL-12 or CD27/OX40, may drive the induction of antigen-specific CD8 ϩ T cells that are of the Tem phenotype (63,65,66). Previous studies have demonstrated that IL-12 is induced in IFN-AR1 Ϫ/Ϫ mice during LCMV infection and substitutes for the lack of type I IFNs in driving an IFN-␥ response (67).…”

Section: Discussionmentioning

confidence: 99%

Kinetic and Phenotypic Analysis of CD8 ⁺ T Cell Responses after Priming with Alphavirus Replicons and Homologous or Heterologous Booster Immunizations

Knudsen

Ljungberg

Kakoulidou

et al. 2014

J Virol

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Alphavirus replicons are potent inducers of CD8؉ T cell responses and thus constitute an attractive vaccine vector platform for developing novel vaccines. However, the kinetics and memory phenotype of CD8 ؉ T cell responses induced by alphavirus replicons are not well characterized. Furthermore, little is known how priming with alphavirus replicons affects booster immune responses induced by other vaccine modalities. We demonstrate here that a single immunization with an alphavirus replicon, administered as viral particles or naked DNA, induced an antigen-specific CD8 ؉ T cell response that had a sharp peak, followed by a rapid contraction. Administering a homologous boost before contraction had occurred did not further increase the response. In contrast, boosting after contraction when CD8؉ IMPORTANCEAlphavirus replicons are promising vaccine candidates against a number of diseases and are by themselves developed as vaccines against, for example, Chikungunya virus infection. Replicons are also considered to be used for priming, followed by booster immunization using different vaccine modalities. In order to rationally design prime-boost immunization schedules with these vectors, characterization of the magnitude and phenotype of CD8 ؉ T cell responses induced by alphavirus replicons is needed. Here, we demonstrate how factors such as timing and dose affect the phenotypes of memory T cell populations induced by immunization with alphavirus replicons. These findings are important for designing future clinical trials with alphaviruses, since they can be used to tailor vaccination regimens in order to induce a CD8 ؉ T cell response that is optimal for control and/or clearance of a specific pathogen.

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“…IL-12 is well documented to serve as so-called signal 3 cytokine, capable of facilitating CD8 + T cell proliferation, effector functions, and memory formation (28). Therefore, it was not surprising that IL-12 secretion by LSECs could induce T cell immunity.…”

Section: Discussionmentioning

confidence: 99%

TLR1/2 Ligand–Stimulated Mouse Liver Endothelial Cells Secrete IL-12 and Trigger CD8+ T Cell Immunity In Vitro

Liu

Jiang

et al. 2013

The Journal of Immunology

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Liver sinusoidal endothelial cells (LSECs) are unique organ-resident APCs capable of Ag cross-presentation and subsequent tolerization of naive CD8+ T cells. Under certain conditions, LSECs can switch from a tolerogenic to an immunogenic state and promote the development of T cell immunity. However, little is known about the mechanisms of LSECs to induce T cell immunity. In this study, we investigated whether functional maturation of LSECs can be achieved by TLR ligand stimulation and elucidated the mechanisms involved in LSEC-induced T cell immunity. We demonstrate that pretreatment of LSECs with palmitoyl-3-cysteine-serine-lysine-4 (P3C; TLR1/2 ligand) but not poly(I:C) (TLR3 ligand) or LPS (TLR4 ligand) reverted their suppressive properties to induce T cell immunity. Importantly, P3C stimulation caused functional maturation of Ag-presenting LSECs and enabled them to activate virus-specific CD8+ T cells. The LSEC-mediated CD8+ T cell immunity was initiated by soluble mediators, one of which was IL-12 secreted at a low but sustained level after P3C stimulation. P3C stimulation did not induce programmed death ligand 1 expression on LSECs, thereby favoring T cell proliferation and activation instead of suppression. Our data suggest that LSECs undergo maturation exclusively in response to TLR1/2 ligand stimulation and that the immunological status of LSECs was dependent upon the balance between programmed death ligand 1 and IL-12 expression. These results have implications for our understanding of liver-specific tolerance and autoimmunity and for the development of strategies to overcome T cell tolerance in situations such as chronic viral liver infections or liver cancer.

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An alternative signal 3: CD8+ T cell memory independent of IL-12 and type I IFN is dependent on CD27/OX40 signaling

Cited by 26 publications

References 46 publications

IL-27 is required for shaping the magnitude, affinity distribution, and memory of T cells responding to subunit immunization

IL-27 is required for shaping the magnitude, affinity distribution, and memory of T cells responding to subunit immunization

Kinetic and Phenotypic Analysis of CD8 ⁺ T Cell Responses after Priming with Alphavirus Replicons and Homologous or Heterologous Booster Immunizations

TLR1/2 Ligand–Stimulated Mouse Liver Endothelial Cells Secrete IL-12 and Trigger CD8+ T Cell Immunity In Vitro

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An alternative signal 3: CD8+ T cell memory independent of IL-12 and type I IFN is dependent on CD27/OX40 signaling

Cited by 26 publications

References 46 publications

IL-27 is required for shaping the magnitude, affinity distribution, and memory of T cells responding to subunit immunization

IL-27 is required for shaping the magnitude, affinity distribution, and memory of T cells responding to subunit immunization

Kinetic and Phenotypic Analysis of CD8 + T Cell Responses after Priming with Alphavirus Replicons and Homologous or Heterologous Booster Immunizations

TLR1/2 Ligand–Stimulated Mouse Liver Endothelial Cells Secrete IL-12 and Trigger CD8+ T Cell Immunity In Vitro

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Kinetic and Phenotypic Analysis of CD8 ⁺ T Cell Responses after Priming with Alphavirus Replicons and Homologous or Heterologous Booster Immunizations