IFN-αβ Promote Priming of Antigen-Specific CD8+ and CD4+ T Lymphocytes by Immunostimulatory DNA-Based Vaccines

Cho, Hearn Jay; Hayashi, Tomoko; Datta, Sandip K.; Takabayashi, Kenji; Uden, John H. Van; Horner, Anthony A.; Corr, Maripat

doi:10.4049/jimmunol.168.10.4907

Cited by 104 publications

(89 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…7,8 Recent studies demonstrated that IFN-a promotes crosspriming by increasing the expression of Transporters associated with Antigen Processing (TAP)-1 in DCs. 9 In addition, a critical role of type I IFNs in crosspriming of antigen-specific CTLs was directly demonstrated using IFN-a/b receptor-deficient mice. 8 Type I IFNs also directly inhibit proliferation of neoplastic cells through various mechanisms including induction of apoptotic cell death.…”

Section: Introductionmentioning

confidence: 99%

Sequential delivery of interferon-α gene and DCs to intracranial gliomas promotes an effective antitumor response

et al. 2004

View full text Add to dashboard Cite

Effective presentation of tumor antigens by dendritic cells (DCs) is considered to be essential for the induction of antitumor T-cell responses. Apoptotic and necrotic tumors have been noted to be a robust antigen source for DCs. Because glioma cells undergo apoptosis after transfection with the type I interferon (IFN) gene and type I IFNs promote the stimulatory activity of DCs, we hypothesized that transfection of glioma cells with type I IFN genes and provision of DCs would promote particularly effective antitumor activity by both facilitating apoptosis of glioma cells and the presentation of the glioma antigens, thereby inducing specific immune responses against glioma cells. We have previously reported the proof of this hypothesis in vitro and in a subcutaneous tumor model. Here we report an extension of this approach in intracranial (i.c.) gliomas using adenoviral IFN-a (Ad-IFN-a) vector. Mice bearing day-5 i.c. GL261 glioma received sequential intratumoral (i.t.) delivery of Ad-IFN-a and bone marrow-derived syngeneic DCs. This treatment prolonged survival in that nine of 17 animals survived long term (460 days versus 0 of 10 control animals). Specific CTL activity was demonstrated following this regimen in the cervical lymph nodes, and the therapeutic efficacy was dependent upon CD8+ cells. Furthermore, these animals were protected against subsequent rechallenge with GL261 gliomas. DCs injected i.t. survived in the tumor and migrated into cervical lymph node. In vitro migration assays revealed the ability of DCs to migrate toward the tumor, suggesting that i.t. injected DCs migrate through the glioma. Taken together, this combination of gene therapy and cellular immunotherapy may be an effective future strategy for treating human gliomas.

show abstract

Section: Introductionmentioning

confidence: 99%

Sequential delivery of interferon-α gene and DCs to intracranial gliomas promotes an effective antitumor response

et al. 2004

View full text Add to dashboard Cite

show abstract

“…Several recent reports indicate that the ability to cross-prime CD8 ϩ T cell responses is linked to induction of type I IFN production (48,55,56). Therefore, to determine whether a similar association was true with LANAC-based vaccines, we examined the ability of different liposome-TLR agonist complexes to induce production of IFN-␣ in vivo.…”

Section: Adjuvants Prepared With Tlr9 or Tlr3 Agonists Effectively Crmentioning

confidence: 99%

Efficient Immunization and Cross-Priming by Vaccine Adjuvants Containing TLR3 or TLR9 Agonists Complexed to Cationic Liposomes

Zaks

Jordan

Guth³

et al. 2006

The Journal of Immunology

227

187

View full text Add to dashboard Cite

Complexing TLR9 agonists such as plasmid DNA to cationic liposomes markedly potentiates their ability to activate innate immunity. We therefore reasoned that liposomes complexed with DNA or other TLR agonists could be used as effective vaccine adjuvants. To test this hypothesis, the vaccine adjuvant effects of liposomes complexed to TLR agonists were assessed in mice. We found that liposomes complexed to nucleic acids (liposome-Ag-nucleic acid complexes; LANAC) were particularly effective adjuvants for eliciting CD4+ and CD8+ T cell responses against peptide and protein Ags. Notably, LANAC containing TLR3 or TLR9 agonists effectively cross-primed CD8+ T cell responses against even low doses of protein Ags, and this effect was independent of CD4+ T cell help. Ag-specific CD8+ T cells elicited by LANAC adjuvants were functionally active and persisted for long periods of time in tissues. In a therapeutic tumor vaccine model, immunization with the melanoma peptide trp2 and LANAC adjuvant controlled the growth of established B16 melanoma tumors. In a prophylactic vaccine model, immunization with the Mycobacterium tuberculosis protein ESAT-6 with LANAC adjuvant elicited significant protective immunity against aerosol challenge with virulent M. tuberculosis. These results suggest that certain TLR agonists can be combined with cationic liposomes to produce uniquely effective vaccine adjuvants capable of eliciting strong T cell responses against protein and peptide Ags.

show abstract

“…In vitro stimulation of BM-derived DC from wt mice with CpG induced increased surface expression of CD40, CD86, and MHC class I. In contrast, only a subpopulation of BM-derived DC derived from IFN-a/bR À/À mice was capable of upregulating CD40 and CD80 in response to CpG [25]. Other in vitro data show that IFN-a/b promotes the upregulation of the costimulatory molecule CD86 [23].…”

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

“…Furthermore, the ability of DC to crosspresent exogenous model antigens such as OVA in the presence of TLR ligands to CD8 1 T cells has been shown to depend on IFN-a/b receptor (IFN-a/bR) signaling. Thus, both MyD88 as well as type I IFN signaling has been shown to be important for the crosspresentation of exogenous model antigens [25][26][27][28][29].VLP as non-replicating antigens need to be cross-presented in order to prime CD8 1 T cells. We have previously shown that the immuno-dominant H-2D b restricted lymphocytic choriomeningitis virus (LCMV)-glycoprotein-derived peptide p33 coupled to VLP is efficiently cross-presented by both DC and macrophages.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Innate signaling regulates cross‐priming at the level of DC licensing and not antigen presentation

Keller¹,

Schwarz²,

Manolova³

et al. 2009

Eur J Immunol

View full text Add to dashboard Cite

Innate stimuli, such as TLR ligands, are known to greatly facilitate cross-priming. Currently it is unclear whether innate stimuli enhance cross-priming at the level of crosspresentation or at the level of T-cell priming. In this study, we addressed this question by measuring cross-presentation as well as cross-priming by virus-like particles (VLP) displaying peptide p33 derived of lymphocytic choriomeningitis virus. Innate stimuli were varied by either packaging different TLR ligands into virus-like particles or using mice deficient in two key molecules of TLR-signaling, namely the adaptor molecule MyD88 as well as IFN-a/b receptor. While efficient cross-presentation occurred despite strongly reduced activation of DC in the absence of TLR ligand-mediated signals, T-cell priming was abolished. Thus, innate stimuli regulate cross-priming at the level of DC licensing for T-cell activation and not antigen presentation.Key words: Antigen presentation/processing . Cross-presentation/priming . DC Introduction CD8 1 T cells play an important role in defense against infectious agents. Activated CD8 1 T cells differentiate into CTL that kill infected cells. CTL recognize endogenously synthesized antigenic peptides complexed with MHC class I molecules on the surface of APC. Since not all pathogens directly infect APC, it is necessary that APC are able to internalize exogenous antigens and present them on MHC class I molecules for CD8 1 T-cell recognition, a process known as cross-presentation [1][2][3]. Such cross-presented antigens may make an important contribution to the induction of CTL responses, in particular for non-replicating antigens, such as virus-like particles (VLP) [4]. The main cell types involved in cross-presentation are professional APC, such as DC [5,6] as well as macrophages [7,8] but not B cells [9].The primary function of immature DC is to sample foreign antigens for T-cell and perhaps B-cell priming. To this end, DC either sit at strategic positions within lymphoid organs or act as sentinels in peripheral tissues. In any event, for optimal T-cell priming, DC need pathogen-derived signals in order to mature [10]. In a first step, DC are activated by various pathogen-derived molecules (known as PAMP), including ligands for TLR, lectins, intracellular nucleotide-binding oligomerization domain receptors or retinoic acid induced gene [11][12][13][14]. So far 11 TLR have been identified in mice [15]. TLR recognize invariant viral or bacterial structures. A number of receptors are specialized in recognizing nucleic acids, such as dsRNA (TLR3), ssRNA (TLR7 and TLR8), and DNA rich in non-methlylated CG motifs (CpG, TLR9). The interaction of microbial ligands with innate immune system receptors initiates the maturation of DC. Stimulation of DC with such innate stimuli results in licensed DC. Such DC express intermediate levels of cell surface costimulatory molecules. Endogenous mediators, such as TNF family members, chemokines, or other cytokines facilitate the full differentiation of DC, expressing high leve...

show abstract

IFN-αβ Promote Priming of Antigen-Specific CD8+ and CD4+ T Lymphocytes by Immunostimulatory DNA-Based Vaccines

Cited by 104 publications

References 46 publications

Sequential delivery of interferon-α gene and DCs to intracranial gliomas promotes an effective antitumor response

Sequential delivery of interferon-α gene and DCs to intracranial gliomas promotes an effective antitumor response

Efficient Immunization and Cross-Priming by Vaccine Adjuvants Containing TLR3 or TLR9 Agonists Complexed to Cationic Liposomes

Innate signaling regulates cross‐priming at the level of DC licensing and not antigen presentation

Contact Info

Product

Resources

About