Dendritic cells matured by a prostaglandin E2-containing cocktail can produce high levels of IL-12p70 and are more mature and Th1-biased than dendritic cells treated with TNF-α or LPS

Landi, Abdolamir; Babiuk, Lorne A.; Hurk, Sylvia van Drunen Littel‐van den

doi:10.1016/j.imbio.2010.11.004

Cited by 31 publications

(28 citation statements)

References 79 publications

(107 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…PGE 2 plays a key role in the modulation of innate [29, 43, 61] as well as adaptive immune responses [62–64] and provides additional characterization of age- and adjuvant-specific differences in leukocyte activation. Of note, adjuvant-induced PGE 2 induction by the monomac6 monocytic cell-line tested in vitro has been linked to reactogenicity in vivo [36], though it has yet to be established that PGE 2 serves as a reactogenicity biomarker in other in vitro model systems, such as whole blood [65].…”

Section: Discussionmentioning

confidence: 99%

In vitro cytokine induction by TLR-activating vaccine adjuvants in human blood varies by age and adjuvant

et al. 2016

View full text Add to dashboard Cite

Most infections occur in early life, prompting development of novel adjuvanted vaccines to protect newborns and infants. Several Toll-like receptor (TLR) agonists (TLRAs) are components of licensed vaccine formulations or are in development as candidate adjuvants. However, the type and magnitude of immune responses to TLRAs may vary with the TLR activated as well as age and geographic location. Most notably, in newborns, as compared to adults, the immune response to TLRAs is polarized with lower Th1 cytokine production and robust Th2 and anti-inflammatory cytokine production. The ontogeny of TLR-mediated cytokine responses in international cohorts has been reported, but no study has compared cytokine responses to TLRAs between U.S. neonates and infants at the age of 6 months. Both are critical age groups for the currently pediatric vaccine schedule. In this study, we report quantitative differences in the production of a panel of 14 cytokines and chemokines after in vitro stimulation of newborn cord blood and infant and adult peripheral blood with agonists of TLR4, including monophosphoryl lipid A (MPLA) and glucopyranosyl lipid Adjuvant aqueous formulation (GLA-AF), as well as agonists of TLR7/8 (R848) and TLR9 (CpG). Both TLR4 agonists, MPLA and GLA-AF, induced greater concentrations of Th1 cytokines CXCL10, TNF and Interleukin (IL)-12p70 in infant and adult blood compared to newborn blood. All the tested TLRAs induced greater infant IFN-α2 production compared to newborn and adult blood. In contrast, CpG induced greater IFN-γ, IL-1β, IL-4, IL-12p40, IL-10 and CXCL8 in newborn than infant and adult blood. Overall, to the extent that these in vitro studies mirror responses in vivo, our study demonstrates distinct age-specific effects of TLRAs that may inform their development as candidate adjuvants for early life vaccines.

show abstract

Section: Discussionmentioning

confidence: 99%

In vitro cytokine induction by TLR-activating vaccine adjuvants in human blood varies by age and adjuvant

et al. 2016

View full text Add to dashboard Cite

show abstract

“…In general, PGE 2 inhibits Th1-polarizing cytokine production by DCs and macrophages, changes DC morphology, resulting in a loss of podosome formation and co-stimulatory receptor expression (99–101). Paradoxically, PGE 2 may also increase production of Th1-polarizing cytokines and DC function (213, 214). These apparently conflicting in vitro activities may be due to distinct effects that PGE 2 exerts over time and at different DC:T cell ratios in co-culture (215, 216), as PGE2 can also act directly on CD4 + T cells, promoting the expansion of Th1 and Th17 cells (217).…”

Section: Lipids and Lipid-type Moleculesmentioning

confidence: 99%

Soluble Mediators Regulating Immunity in Early Life

2014

View full text Add to dashboard Cite

Soluble factors in blood plasma have a substantial impact on both the innate and adaptive immune responses. The complement system, antibodies, and anti-microbial proteins and peptides can directly interact with potential pathogens, protecting against systemic infection. Levels of these innate effector proteins are generally lower in neonatal circulation at term delivery than in adults, and lower still at preterm delivery. The extracellular environment also has a critical influence on immune cell maturation, activation, and effector functions, and many of the factors in plasma, including hormones, vitamins, and purines, have been shown to influence these processes for leukocytes of both the innate and adaptive immune systems. The ontogeny of plasma factors can be viewed in the context of a lower effectiveness of immune responses to infection and immunization in early life, which may be influenced by the striking neonatal deficiency of complement system proteins or enhanced neonatal production of the anti-inflammatory cytokine IL-10, among other ontogenic differences. Accordingly, we survey here a number of soluble mediators in plasma for which age-dependent differences in abundance may influence the ontogeny of immune function, particularly direct innate interaction and skewing of adaptive lymphocyte activity in response to infectious microorganisms and adjuvanted vaccines.

show abstract

“…However, other investigators justify and encourage the use of PGE 2 in DC maturation cocktails. 137,147,148 Zobywalski et al 137 compared various maturation cocktails and concluded that the best one (with respect to DC phenotype, maturation stability, allostimulatory function ,and recovery after cryopreservation) is a combination of IL-1β, TNF-α, IFN-γ, low-dose PGE 2 , and resiquimod (R848, a synthetic TLR7/8 agonist), defined as the Zobywalski cocktail. The generated DCs are nonexhausted, secrete substantial amounts of IL-12p70 (albeit considerably less compared with Kalinski DCs), and show very high CCR7 expression, which is equal to that of Jonuleit DCs.…”

Section: Pge 2 In DC Maturation Cocktails: a Foe Or A Friend?mentioning

confidence: 99%

Therapeutic Dendritic Cell-Based Cancer Vaccines: The State of the Art

et al. 2013

View full text Add to dashboard Cite

Dendritic cells (DCs) are the most potent professional antigen-presenting cells, capable of initiating proper adaptive immune responses. Although tumor-infiltrating DCs are able to recognize cancer cells and uptake tumor antigens, they often have impaired functions because of the immunosuppressive tumor milieu. Therefore, DCs are targeted by therapeutic means either in vivo or ex vivo to facilitate tumor antigen presentation to T cells and induce or promote efficient antitumor immune responses in cancer patients. This immunotherapeutical approach is defined as specific active tumor immunotherapy or therapeutic cancer vaccination. In this review we briefly discuss general aspects of DC biology, followed by a thorough description of the current knowledge and optimization trends of DC vaccine production ex vivo, including various approaches for the induction of proper DC maturation and efficient loading with tumor antigens. We also discuss critical clinical aspects of DC vaccine application in cancer patients, including protocols of administration (routes and regimens), individualization of tumor immunotherapy, prediction and proper evaluation of immune and clinical responses to immunotherapy, and the critical role of combining tumor immunotherapy with other cancer treatment strategies to achieve maximal therapeutic effects.

show abstract

Dendritic cells matured by a prostaglandin E2-containing cocktail can produce high levels of IL-12p70 and are more mature and Th1-biased than dendritic cells treated with TNF-α or LPS

Cited by 31 publications

References 79 publications

In vitro cytokine induction by TLR-activating vaccine adjuvants in human blood varies by age and adjuvant

In vitro cytokine induction by TLR-activating vaccine adjuvants in human blood varies by age and adjuvant

Soluble Mediators Regulating Immunity in Early Life

Therapeutic Dendritic Cell-Based Cancer Vaccines: The State of the Art

Contact Info

Product

Resources

About