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Ulva, an edible green alga, contains sulfated polysaccharides and oligosaccharides that possess immunomodulatory and anti-inflammatory properties. The objective of this study was to investigate the anti-allergic effects of Ulva-derived samples of polysaccharides (UP), oligosaccharides (UO), and residues (UR) on delayed-type hypersensitivity (DTH) in mice. Oral treatment of mice with UP, UO, and UR (250 mg/kg body weight) daily noticeably improved the DTH reaction as evidenced by attenuation of footpad swelling and cell infiltration at the allergen-challenge site. Although the Ulva samples had limited impacts on the production of serum total IgG, decreased concentrations of allergen-specific IgG and IgG2a and an increased concentration of IgG1 were observed in the treated mice. Moreover, treatment with them suppressed allergen-induced IFN-γ and TNF-α secretion and elevated IL-4 secretion. However, none of the Ulva sample treatments could modulate the production of IL-10. Concordantly, the in situ data reveal that the Ulva sample treatments suppressed IFN-γ and TNF-α expression at the allergen-injection site. These findings collectively suggest the potential of UP, UO, and UR as functional food candidates for the management of delayed-type hypersensitivity. [ABSTRACT FROM AUTHOR]

Several recent papers support the involvement of an interaction between stromal cell-derived factor-1 (SDF-1/CXCL12) and its receptor, chemokine receptor CXCR4, in memory T cell migration in the inflamed rheumatoid arthritis (RA) synovium. Analogs of the 14-mer peptide T140 were previously found to be specific CXCR4 antagonists that were characterized as not only HIV-entry inhibitors but also anti-cancer-metastatic agents. In this study, a T140 analog, 4F-benzoyl-TN14003, was proven to inhibit CXCL12-mediated migration of human Jurkat cells and mouse splenocyte in a dose-dependent manner in vitro (IC50=0.65 and 0.54 nM, respectively). Furthermore, slow release administration by subcutaneous injection (s.c.) of 4F-benzoyl-TN14003 using an Alzet osmotic pump significantly suppressed the delayed-type hypersensitivity response induced by sheep red blood cells in mice, and significantly ameliorated clinical severity in collagen-induced arthritis in mice. As such, T140 analogs might be attractive lead compounds for chemotherapy of RA. [Copyright &y& Elsevier]

The evolution and maintenance of conspicuous phenotypic polymorphisms has challenged evolutionary ecologists for centuries. Polymorphisms in pleiotropic cascades or genetic linkage may lead to correlations of life history traits such as immunity, parasite infection levels, pigmentation and lifetime reproductive success. The common buzzard Buteo buteo is a bird of prey occurring in several plumage morphs, which differ in pigmentation and in the prevalence, infection intensity and clone composition of their most common blood parasite, as well as in ectoparasite infestation levels. Buzzard morphs are heritable and exhibit a heterozygote advantage where intermediates have higher lifetime reproductive success (LRS). We explored the hypothesis that the differences in pigmentation also correspond to differences in immunity. We hence compared an inducible adaptive and an innate constitutive immune response between the buzzard plumage morphs. The increase of specific anti-tetanus antibodies after vaccination was explained by the morph of the nestling's mother and was highest in offspring of intermediate mothers. Additionally, nestlings with higher humoral response were less infected with blood parasites and, if infected, harboured a lower genetic diversity of these parasites. The phytohaemagglutinin-induced skin swelling, a complex of cellular inflammatory responses, was lowest in intermediate nestlings. The higher LRS of intermediate buzzards suggests that the cellular immunity is an inferior fitness determinant compared to humoral immunity. The strength of immune responses was not linear along the melanisation gradient, indicating that there is most likely no simple genetic correlation between immune responses and plumage morphs. [ABSTRACT FROM AUTHOR]

Background: Parasite-derived molecules with immunomodulatory properties, which have been optimised during host-parasite co-evolution, exhibit potential applications as novel immunotherapeutics. We have previously demonstrated that Schistosoma japonicum HSP60-derived peptide SJMHE1 induces CD4+CD25+ regulatory T-cells (Tregs) and that adoptively transferred SJMHE1-induced CD4+CD25+ Tregs inhibit delayed-type hypersensitivity (DTH) in mice. However, multiple concerns regarding this method render this treatment unsuitable. To gain further insights into the potential effects of SJMHE1, we used ovalbumin (OVA)-induced DTH and evaluated the effect of SJMHE1 on DTH mice. Methods: BALB/c mice were sensitised with OVA alone or combined with SJMHE1 and then challenged with OVA to induce DTH. We first analysed the potential effects of SJMHE1 by measuring DTH responses, T-cell responses, cytokine secretion, and Treg proportions. We then evaluated the expression levels of IL-10 and TGF-β1 in CD4+CD25+ T-cells during DTH and Treg generation to identify the mechanism by which SJMHE1 suppresses DTH. Results: SJMHE1 modulated the effector response against OVA-induced DTH and stimulated the production of the anti-inflammatory cytokines IL-10 and TGF-β1 in immunised mice through a mechanism involving CD4+CD25+ Tregs. SJMHE1-induced CD4+CD25+ Tregs expressed high levels of CTLA-4, IL-10, and TGF-β1, which substantially contributed to the suppressive activity during DTH. The administration of SJMHE1 to DTH in mice led to the expansion of CD4+CD25+ Tregs from CD4+CD25- T-cells in the periphery, which inhibited DTH responses. Conclusions: Our study proves that the parasite-driven peptide suppresses DTH in mice, which may confer a new option for inflammation treatment. [ABSTRACT FROM AUTHOR]

Peridinin and fucoxanthin, which are natural carotenoids isolated from a symbiotic dinoflagellate, Symbiodinium sp., and a brown alga, Petalonia fascia, respectively, were compared for inhibitory effects on delayed-type hypersensitivity in mice. The number of eosinophils at the site of inflammation and in peripheral blood was compared for the administration of peridinin and fucoxanthin applied by painting and intraperitoneally. Peridinin, but not the structurally-related fucoxanthin, significantly suppressed the number of eosinophils in both the ear lobe and peripheral blood. Furthermore, peridinin applied topically, but not administered intraperitoneally, suppressed the level of eotaxin in the ears of sensitized mice. Fucoxanthin weakly suppressed the concentration of eotaxin in ears only by intraperitoneal administration. Although both carotenoids inhibited the migration of eosinophils toward eotaxin, the inhibitory effect of peridinin was higher than that of fucoxanthin. Peridinin may be a potential agent for suppressing allergic inflammatory responses, such as atopic dermatitis, in which eosinophils play a major role in the increase of inflammation. [ABSTRACT FROM AUTHOR]

Background: Immune perturbation likely affects the development of Kaposi sarcoma (KS) among people infected with the KS-associated herpesvirus (KSHV). We tested whether KSHV-seropositive individuals or cases of classic KS (cKS), which typically originates in the leg, had differing delayed-type hypersensitivity (DTH) in the forearm or leg.Methods: Mantoux DTH with three antigens (Candida, tetanus, PPD) was performed on the forearm and leg of 15 cKS cases, 14 KSHV-positives without KS, and 15 KSHV-negative controls. The diameters of induration responses were compared by group and body site.Results: Leg DTH was greater than forearm DTH among controls (mean difference 5.6 mm, P=0.0004), whereas this was not observed in cKS cases (-2.2 mm, P=0.32) or KSHV-positives (0.5 mm, P=0.56). Leg-minus-forearm DTH difference was greater in controls compared with cKS cases (P=0.004) and KSHV-positives (P=0.002). Leg-plus-forearm DTH was similar in controls (mean 28.2 mm) and cKS cases (24.5 mm, P=0.60), but it was reduced in KSHV-positives (11.8 mm, P=0.02), particularly in the leg (P=0.004) and marginally in the forearm (P=0.07).Conclusion: KS cases had weaker DTH only in the leg, whereas both body sites appeared weaker in KSHV-positives without KS. Both systemic and regional immune alterations may influence the development of this malignancy. [ABSTRACT FROM AUTHOR]

AbstractAim:To investigate the immunosuppressive effect of gossypol in mice both in vitro and in vivo.Methods:The in vitro effect of gossypol on the proliferation of lymphocytes isolated from lymph nodes of BALB/c mice was determined by CFSE staining and by an MTS assay. Lymphocyte activation and lymphoblastic transformation were evaluated with immunostaining. Cell apoptosis was detected by Annexin-V and Hoechst 33342 staining. The in vivo immunosuppressive effect of gossypol on the DTH reaction was evaluated using a mouse DTH model induced by 2,4-dinitro-1-fluorobenzene (DNFB). The thickness of the ears was measured, and the histological changes of the mouse auricles were observed after hematoxylin-eosin staining. The proliferation capacity of lymphocytes from DTH mice was also assayed.Results:In vitro, gossypol could significantly inhibit the proliferation of mouse lymphocytes stimulated with phorbol ester plus ionomycin in a dose-dependent manner. Although the expression of the early activation antigen CD69 was not affected, the lymphoblastic transformation of both T and B lymphocyte subsets was significantly suppressed by gossypol. Moreover, gossypol could induce apoptosis of lymphocytes, and the effect was time- and dose-dependent. In vivo, the DTH reaction in mice was markedly alleviated by gossypol injected intraperitoneally. Lymphocytes from drug-treated DTH mice had a reduced proliferation capacity as compared with lymphocytes from untreated DTH mice. Gossypol treatment also markedly reduced the number of infiltrated lymphocytes in the auricles of DTH mice.ConclusionGossypol exhibited immunosuppressive effects in mice, probably by inhibition of lymphocyte proliferation and by induction of cell apoptosis.Acta Pharmacologica Sinica (2009) 30: 597–604; doi: 10.1038/aps.2009.35; published online 13th April 2009 [ABSTRACT FROM AUTHOR]

Previously, the delayed-type hypersensitivity (DTH) cutaneous test with the spike protein of SARS-CoV-2 has been shown to be a simple in vivo method to measure T-cell functionality after natural infection and in vaccinated individuals. Methods: Twenty-five kidney-transplanted recipients were immunized with two doses of the mRNA-based Pfizer–BioNTech COVID19 vaccine three weeks apart. Cell-immune response (CIR) was evaluated ten weeks later using an in vivo DTH skin test and in vitro with an interferon gamma release assay (IGRA). Humoral Immune Response (HIR) was determined by the measurement of specific IgG anti-S1 SARS-CoV-2. Results: Ten weeks after the second dose of the vaccine, 23 out of 25 transplanted patients had a positive DTH skin test, while in vitro CIR was considered positive in 20 patients. Unspecific stimulation was positive in all 25 patients, showing no T-cell defect. Seven out of twenty-five patients had a negative specific anti-spike IgG. CIR was positive in all immune-competent control patients. Conclusions: DTH is a useful, simple, and cheaper tool that can be used to assess cellular immune response, with an excellent correlation with the in vitro CIR. CIR assessment after vaccination in these immunocompromised patients is an excellent complement to HIR-based methods. This skin test could be used if classical in vitro methods cannot be applied. [ABSTRACT FROM AUTHOR]

Background and Purpose: Our aim was to examine the effect of demethylnobiletin on various experimental models of delayed-type hypersensitivity (DTH) reactions and to determine its influence on the mediators and enzymes involved in these reactions.Experimental Approach: DTH was induced in mice by oxazolone, dinitrofluorobenzene (DNFB) and sheep red blood cells (SRBC). The effect of demethylnobiletin on the ensuing DTH was studied, especially in relation to oedema formation, cell infiltration and tissue damage. Its activity on different mediators implicated in DTH reactions was also determined and its effect on nitric oxide synthase (NOS)-2 analysed. Finally, its influence on T lymphocyte proliferation, apoptosis and caspase 3 activity was tested.Key Results: DTH reactions were all reduced by demethylnobiletin. The experimental results suggest that the compound may act by reducing cell infiltration and by suppressing mediators such as interleukin-2 (IC50=1.63 microM), interleukin-4 (IC50=2.76 microM), tumour necrosis factor-alpha (IC50=0.66 microM), interferon-gamma (IC50=1.35 microM), and interleukin-1 beta (46% at 2.5 microM) and by concomitantly increasing the production of the anti-inflammatory cytokine, interleukin-10. In addition, while demethylnobiletin affected nitric oxide production, it did not modify NOS-2 expression. Finally, demethylnobiletin inhibited proliferation of T cells and induced their apoptosis.Conclusions and Implications: Demethylnobiletin decreased DTH reactions induced by various agents. This finding, along with the fact that the compound has a low toxicity and exhibits several other interesting properties, could pave the way for other structurally related citroflavonoids to be used as pharmacological agents in complementary therapies. [ABSTRACT FROM AUTHOR]

The mechanism by which dermal cells expressing a macrophage calcium-type lectin (MGL) trafficked to regional lymph nodes was investigated. Conditioned medium prepared from organ cultures of mouse skin sensitized with a mixture of acetone and dibutylphthalate was shown to decrease the number of MGL+ cells in the dermis in ex vivo organ culture assays. In in vitro culture of sensitized skin, the loss of MGL+ cells was abrogated by the addition to the culture medium of mAb against IL-1β, while addition of recombinant IL-1β to the medium in which untreated skin was cultured induced loss of MGL+ cells. Intradermal injection of recombinant IL-1β also resulted in a transient increase of MGL+ cells in the T cell area of draining lymph nodes in vivo, indicating that IL-1β is central in the entire process of MGL+ cell trafficking to the lymph nodes. Supporting this is that cells producing IL-1β were detected in the epidermis of cultured skin even early after sensitization. The possibility that IL-1β simply down-regulates MGL expression was eliminated by Western blotting experiments with isolated MGL+ cells treated with or without IL-1β. IL-1α and tumor necrosis factor (TNF)-α were also able to induce migration of MGL+ cells in the ex vivo assay in a manner akin to IL-1β, and antibodies against them abrogated this. Isolated MGL+ cells from skin cultured in type I collagen matrix in vitro displayed morphological changes upon exposure to IL-1β, IL-1α or TNF-α, indicating that these cytokines exert a direct effect on these cells. Thus, pro-inflammatory cytokines, particularly IL-1β, are produced at the site of skin sensitization and are involved in at least initiating the trafficking of cells expressing MGL to the lymph nodes. [ABSTRACT FROM PUBLISHER]

Deoxynivalenol (DON), a highly prevalent mycotoxin food contaminant, is known to have immunotoxic effects. In the current study, the potential of dietary interventions with specific mixtures of trans-galactosyl-oligosaccharides (TOS) to alleviate these effects were assessed in a murine influenza vaccination model. Vaccine-specific immune responses were measured in C57Bl/6JOlaHsd mice fed diets containing DON, TOS or a combination, starting 2 weeks before the first vaccination. The direct effects of TOS and its main oligosaccharide, 3′-galactosyl-lactose (3′-GL), on DON-induced damage were studied in Caco-2 cells, as an in vitro model of the intestinal epithelial barrier. Exposure to DON significantly reduced vaccine-specific immune responses and the percentages of Tbet+ Th1 cells and B cells in the spleen. DON significantly altered epithelial structure and integrity in the ileum and reduced the SCFA levels in the cecum. Adding TOS into DON-containing diets significantly improved vaccine-specific immune responses, restored the immune cell balance in the spleen and increased SCFA concentrations in the cecum. Incubating Caco-2 cells with TOS and 3′-GL in vitro further confirmed their protective effects against DON-induced barrier disruption, supporting immune modulation. Overall, dietary intervention with TOS can attenuate the adverse effects of DON on Th1-mediated immune responses and gut homeostasis. These beneficial properties might be linked to the high levels of 3′-GL in TOS. [ABSTRACT FROM AUTHOR]

Species- or strain-related differences in receptivity of intermediate hosts to E. multitocularis larvae could be related to differences in specific cellular immune response of the host. In order to test this hypothesis, we assessed the delayed-type hypersensitivity (DTH) to E. multilocutaris antigens (EmAg) in mice of three strains differing by their sensitivity (AKR and C57BL.6) or resistance (C57BL.10) to E. multilocutaris infection. DTH was determined by measuring in vivo the foot-pad response 24 h after an EmAg antigenic challenge. The level of positive response was evaluated in immunized mice; however, a typical DTH response was only observed by immunizing mice with a strong adjuvant schedule. Course of DTH in the immunized mice was shown to be somewhat different in sensitive and resistant mice. The differences were much more marked in mice infected with proliferative E. multitocularis larvae. The levels of the footpad response was significantly higher in resistant mice, although the peak of the reaction was obtained later than in sensitive mice, DTH. expressed by the foot-pad response against EmAg remained significant for the entire period of observation in sensitive as well as in resistant mice. There was no correlation between receptivity of the murine hosts and levels of specific antibodies against EmAg. These results suggest a relationship between resistance to E. multitocularis infection and intensity and/or course of DTH in mice. The resistance could be mediated by some particularities of the in situ cellular immune response in the periparasitie granuloma. [ABSTRACT FROM AUTHOR]

Soluble mediators from peripheral blood lymphocytes activated either by skin test antigens or by alloantigens restored the delayed type hypersensitivity (DTH) reaction in the majority of anergic surgical patients who are at increased risk for sepsis and mortality. Antigen had lo be injected together with the mediators and the individual had to be reactive to the antigen for restoration, These results suggest that restoration of the DTH response depends on the ability of cytokines produced and acting in a non-specific manner lo promote the response of the anergic patients' specific antigen-sensitive cells to antigen. [ABSTRACT FROM AUTHOR]

Following one intraperitoneal injection of Suramin (400 mg/kg) in mice, biphasic alterations of the resistance to Listeria monocytogenes were observed, depending on the timing of the drug administration in relation to the intravenous challenge. Treatment with suramin, concomitantly or 1 day before, enhanced markedly the bacterial growth in spleen and liver, detected us early as 3 to 6 h after the challenge, the maximum being observed at 48 h in the liver. In contrast, an increased resistance was observed when suramin was given 8 days before the challenge. This late effect was associated with a stimulation of the mononuclear phagocyte system as measured by the increase of the spleen index and accumulation of histiocytic cells in the lymphoid organs, such as peripheral nodes. Intraperitoneal inoculation of suramin (100 mg/kg), before, during and after an intravenous injection of low dose (2 x 104/mouse) of Mycobacterium bovis (BCG) in C57BL/6 and CH3 mice were followed, in both strains, by a similar increase of the mycobacterial growth in spleen and liver during the first 2 weeks. This indicates that suramin was acting on a different non specific mechanism of resistance than the one being expressed by the Beg gene controlling the natural resistance as described recently. However, when the same schedule of suramin treatment was given lo these two strains, during subcutaneous immunization with 1 x 107 viable BCG, a significant decrease of 48 h delayed-type hypersensitivity to tuberculin was noted 21 days later only in C57BL/6 but not in C3H mice, in which such a reaction was also of low magnitude in the infected control. The decrease of this cell-mediated immunity parameter in C57BL/6 suramin treated mice was also correlated with a higher number of viable BCG found at the challenge site and in the draining nodes. [ABSTRACT FROM AUTHOR]

Aims To evaluate whether patients with late complications of pacemakers or implantable cardioverter-defibrillators have hypersensitivity reactions to some of the materials used in generators or in electrodes, or to environmental metal burden. Methods and results The cohort consisted of 20 men and 4 women (mean age: 62.3 ± 17.2 years) who had a history of late complications of implanted devices. The control group involved 25 men and 8 women (mean age: 64.6 ± 14.0 years) who had comparable devices, but no history of late complications. Lymphocyte transformation test was used to evaluate hypersensitivity to eight metal pollutants (antimony, manganese, mercury, molybdenum, nickel, platinum, tin, and titanium) selected by results of questionnaires on environmental burden, and by material analysis of generators and electrode surfaces. Exposures to metal pollutants were approximately the same in patients and in controls. Titanium alloy used in generators contained at least 99.32% of titanium and trace levels of other metals; higher levels of tin and platinum were detected in electrode surfaces. Hypersensitivity reactions to mercury and tin were significantly more frequent in patients than in controls (patients and controls: mercury: 68.2 and 31.1%, respectively; P  = 0.022; tin: 25.0 and 3.2%, respectively; P  = 0.035). In contrast, hypersensitivity to manganese was significantly more frequent in controls than in patients (patients and controls: 13.6 and 50.0%, respectively; P  = 0.008). Conclusion Our findings suggest a possible relation between hypersensitivity to metals used in implantable devices or to environmental metal burden and the occurrence of their late complications. [ABSTRACT FROM AUTHOR]

Bioassays that predict clinical outcome are essential to optimize cellular anticancer immunotherapy. We have recently developed a robust and simple skin test to evaluate the capacity of tumor-specific T cells to migrate, recognize their targets and exert effector functions. This bioassay detects T cells with an elevated antineoplastic potential and hence rapidly identifies patients responding to immunotherapy. [ABSTRACT FROM PUBLISHER]