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DTH Reactions (dth + reaction)
Selected AbstractsImmunotherapy against metastatic renal cell carcinoma with mature dendritic cellsINTERNATIONAL JOURNAL OF UROLOGY, Issue 4 2007Akihiko Matsumoto Objective: We performed a clinical trial of immunotherapy using autologous mature dendritic cells (DC) pulsed with autologous tumor lysate, for patients with metastatic renal cell carcinoma (RCC). Methods: Patients with refractory metastatic RCC were enrolled in the study. All of them received interferon (IFN)-, treatment after nephrectomy and were followed over 3 months prior to this study. Autologous monocyte-derived immature DC were pulsed with lysate from autologous primary tumor as the antigen and keyhole limpet hemocyanin (KLH) as immunomodulator, and cultured in the presence of tumor necrosis factor (TNF)-,, interleukin (IL)-1,, and prostaglandin (PG)E2 to generate mature DC. Mature DC were injected intradermally near bilateral inguinal lymph nodes of the patients. A delayed-type hypersensitivity (DTH) test and enzyme-linked immunospot (ELISPOT) assay were performed to evaluate the immunological response. After 4 months from first injection, the clinical effect was evaluated by diagnostic imaging. Results: The treatments were well tolerated without significant toxicity by the patients who were an average of 65.7 years old and had multiple metastases in the lung and other organs. One of the two patients developed a positive DTH reaction to tumor lysate and the other patient only to KLH. The patient with a positive DTH reaction to tumor lysate had stable disease in the clinical evaluation. Conclusions: We confirmed the safety of DC therapy in this clinical trial. The DTH test revealed that the DC therapy induced immunological response to RCC. On the other hand, it was necessary to reconsider the patient selection criteria. [source] Dendritic cell immunotherapy for patients with metastatic renal cell carcinoma: University of Tokyo experienceINTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2002Takeshi Azuma Abstract Background : Dendritic cells (DC) are the most potent antigen-presenting cells and induce host antitumor immunity through the T-cell response. A clinical study of immunotherapy using cultured DC loaded with tumor antigen, for patients with metastatic renal cell carcinoma (RCC) was performed. Methods : Dendritic cells were generated by culturing monocytes from peripheral blood for 7 days in the presence of granulocyte,macrophage colony-stimulating factor and interleukin-4. On day 6 the DC were pulsed with lysate from autologous tumor as the antigen and with keyhole limpet hemocyanin (KLH) as immunomodulator. The patients were given four doses of lysate-pulsed DC by intradermal injection with a 2-week interval between doses. Clinical effect and immune response were, respectively, evaluated by radiological examination and delayed-type hypersensitivity (DTH) test. Results : Three patients were enrolled and the immunotherapy was well tolerated without significant toxicity. The vaccination induced a positive DTH reaction to tumor lysate in two patients and to KLH in all patients. Clinical responses consisted of one case of no change and two cases of progression of disease. However, we did not see a significant reduction of tumor volume in any case. Conclusion : Dendritic cell vaccination can safely induce an immunological response against RCC. Further trials are needed to fully evaluate its efficacy. [source] Immunosuppression in the northern leopard frog (Rana pipiens) induced by pesticide exposureENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2003Mary-Kate Gilbertson Abstract An injection study and a field study were used to investigate the hypothesis that environmental xenobiotics have the potential to alter the immune function of northern leopard frogs (Rana pipiens). Three assays, IgM-specific antibody response to keyhole limpet hemocyanin linked to dinitrophenyl (KLH-DNP), zymozan induced chemiluminescence (CL) of whole blood and the delayed-type hypersensitivity (DTH), were used to assay humoral, innate and cell-mediated immune endpoints. Sublethal doses of DDT (923 ng/g wet wt), malathion (990 ng/g wet wt), and dieldrin (50 ng/g wet wt) were used in the injection study. In all pesticide-injected groups, antibody response was dramatically suppressed, DTH reactions were enhanced, and respiratory burst was lower. When the order of administration of pesticides and antigens was reversed, no differences in immune function between the control and dosed groups were apparent, indicating that frogs exposed to pathogens prior to pesticide exposure can still respond. A field study found significant differences in immune function between frog populations in pesticide-exposed and pesticide-free locations. The antibody response and CL were suppressed and the DTH enhanced in frogs from Essex County (ON, Canada). Overall, the results suggest that exposure to these pesticides can cause both stimulatory and suppressive immune changes in adult frogs and is doing so in wild populations. [source] Dendritic cell-derived IL-15 controls the induction of CD8 T,cell immune responsesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2003René Rückert Abstract The development and the differentiation of CD8+ T,cells are dependent on IL-15. Here, we have studied the source and mechanism of how IL-15 modulates CD8+ T,cell-mediated Th1immune responses by employing two delayed-type hypersensitivity (DTH) models. IL-15-deficient (IL-15,/,) mice or mice treated with soluble IL-15R, as an IL-15 antagonist showed significantly reduced CD8+ T,cell-dependent DTH responses, while activation of CD4+ T,cell and B,cell functions remained unaffected. Injection of antigen-labeled dendritic cells (DC) fromIL-15+/+, IL-15,/, or IL-15R,,/, mice revealed that DC-derived IL-15 is an absolute requirement for the initiation of DTH response. The re-establishment of the interaction of IL-15 with the IL-15R, by incubating IL-15,/, DC with IL-15 completely restored the capacity to prime T,cells for DTH induction in vivo. Moreover, IL-15 also enhanced secretion of pro-inflammatory cytokines by DC and triggered in vitro CD8+ T,cell proliferation and IL-2 release. Taken together, the data suggest that an autocrine IL-15/IL-15R, signaling loop in DC is essential for inducing CD8+ -dependent Th1 immune responses in mice. Therefore, targeted manipulation of this loop promises to be an effective, novel strategy for therapeuticmodulation of clinically relevant DTH reactions. [source] Sunscreens containing the broad-spectrum UVA absorber, Mexoryl® SX, prevent the cutaneous detrimental effects of UV exposure: a review of clinical study resultsPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 4 2008Anny Fourtanier Background: UVA exposure of human skin mainly produces reactive oxygen species (ROS) leading to DNA, cell and tissue damage. It alters immune function, pigmentation and it is certainly responsible for a large part of photoaging changes. Moreover UVA is implicated in the etiology of several photodermatoses. As a consequence, to provide adequate protection, sunscreens or skin care products for daily use protective products need UVA absorbers combined with UVB ones. Aim: To assess the efficacy of sunscreens containing a broad-spectrum UVA absorber the Mexoryl® SX or ecamsule and to compare formulations with and without it through a large number of clinical studies in human volunteers and patients. Methods: The following assessments were conducted: ,Prevention of excessive pigmentation induced by UV exposure in Caucasian and Asian skins using a method that measures pigmentation protection factors (PPF). ,Efficacy against DNA damage by measurement of pyrimidine dimer formation and p53 protein accumulation. ,Protection of immune system using delayed type hypersensitivity (DTH) reactions to recall antigens, isomerization of urocanic acid (UCA), alteration of Langerhans cells (LC) density, morphology and function. ,Reduction of epidermal and dermal alterations induced by repeated UVA or UV solar simulated radiation (SSR) using histology or immunohistology. ,Prevention of the polymorphous light eruption (PMLE) in patients prone to develop this disease. Results: Mexoryl® SX-containing formulations showed a dose-dependent level of protection against pigmentation. For a same sun protection factor (SPF) the higher the UVA protection was, the higher was the PPF. Pyrimidine dimer formation and p53 accumulation were significantly reduced by formulations with Mexoryl® SX. In the studies looking at the suppression of DTH reactions to recall antigens by the different UV spectra, the LC alterations and the cis UCA formation, Mexoryl® SX formulations always showed a higher protective potency than sunscreen without it even when the protection against erythema was similar (products with same SPF). Mexoryl® SX formulations also prevented or significantly decreased to minimal, ferritin, tenascin and lysozyme expression induced by repeated UVA or SSR exposure. It also reduced the enhancement of collagenase 2 mRNA expression induced by SSR exposure. Finally PMLE study demonstrated that UVA protection was essential for the prevention of this photodermatose. Conclusion: Mexoryl® SX formulated in sunscreens or daily use products have been shown to be an effective UV absorber, leading to an increased efficacy of these products against a large number of biological damage induced by UVA, SSR or sun exposure. [source] | ||||||||||