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Results for “immunomodulation”

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PubMed1990

Influence of peptide acylation, liposome incorporation, and synthetic immunomodulators on the immunogenicity of a 1-23 peptide of glycoprotein D of herpes simplex virus: implications for subunit vaccines.

A peptide corresponding to residues 1 to 23 of glycoprotein D of herpes simplex virus type 1 was chemically synthesized and coupled to a fatty acid carrier by standard Merrifield synthesis procedures. The resulting peptide-palmitic acid conjugate (acylpeptide) exhibited enhanced immunogenicity in mice as compared with that exhibited by the free form of the peptide. Incorporation of the acylpeptide into liposomes further increased the immunogenicity of the peptide, while inclusion of the immunomodulators muramyl tripeptide phosphatidylethanolamine and monophosphoryl lipid A into the same liposome stimulated the strongest response. The humoral immune responses induced by the acylpeptide-liposome construct were greater than those induced by peptide in Freund complete adjuvant, and cellular responses were equal. The acylpeptide-immunomodulator-liposome formulation also induced significant levels of protective immunity, although the immunity was less than that induced by herpes simplex virus infection. Acylated peptides, especially in liposomes, were taken up more effectively by draining lymph nodes, which possibly accounts in part for the enhanced immunogenicity of the peptides. Since the acylpeptide-immunoliposome formulation used was nontoxic, it could represent a useful way to enhance immunogenicity of subunit peptides used for vaccine purpose in humans and animals.

Acylation↗

PubMed2000

The synthetic immunomodulator murabutide controls human immunodeficiency virus type 1 replication at multiple levels in macrophages and dendritic cells.

Macrophages and dendritic cells are known to play an important role in the establishment and persistence of human immunodeficiency virus (HIV) infection. Besides antiretroviral therapy, several immune-based interventions are being evaluated with the aim of achieving better control of virus replication in reservoir cells. Murabutide is a safe synthetic immunomodulator presenting a capacity to enhance nonspecific resistance against viral infections and to target cells of the reticuloendothelial system. In this study, we have examined the ability of Murabutide to control HIV type 1 (HIV-1) replication in acutely infected monocyte-derived macrophages (MDMs) and dendritic cells (MDDCs). Highly significant suppression of viral replication was consistently observed in Murabutide-treated cultures of both cell types. Murabutide did not affect virus entry, reverse transcriptase activity, or early proviral DNA formation in the cytoplasm of infected cells. However, treated MDMs and MDDCs showed a dramatic reduction in nuclear viral two-long terminal repeat circular form and viral mRNA transcripts. This HIV-1-suppressive activity was not mediated by inhibiting cellular DNA synthesis or by activating p38 mitogen-activated protein kinase. Furthermore, Murabutide-stimulated cells expressed reduced CD4 and CCR5 receptors and secreted high levels of beta-chemokines, although neutralization of the released chemokines did not alter the HIV-1-suppressive activity of Murabutide. These results provide evidence that a clinically acceptable immunomodulator can activate multiple effector pathways in macrophages and in dendritic cells, rendering them nonpermissive for HIV-1 replication.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed2006

Immunomodulating effects of fractioned polysaccharides isolated from Yu-Ping-Feng-Powder in cyclophosphamide-treated mice.

Yu-Ping-Feng-Powder (YP), a traditional Chinese medicine prescription, is widely applied in China for the cure and prevention of diseases related to immunodeficiency. To test whether the fractioned polysaccharides (YPF-P) isolated from YP have immunomodulating activities, the effects of YPF-P on cyclophosphamide (Cy)-treated mice were studied in relation to phagocytosis of macrophage, splenocyte proliferation, and humoral, and cellular immunity parameters. It was found that YPF-P enhances phagocytic activity, augments ConA- or LPS-stimulated T cell proliferation, increases the quantitative haemolysis of SRBC (QHS) and delayed-type hypersensitivity reaction (DTH) to dinitrofluorobenzene. Hence, YPF-P restored the immuno-competence suppressed by Cy. YPF-P also augmented IL-2 and IFN-gamma production, but failed to increase IL-4 production, which indicates that there is high probability that it enhance Th1 function. These results suggested that YPF-P has immunomodulating effects and that the polysaccharides constitute one of the active components of YP.

Administration, Oral↗

PubMed1990

Immunomodulations induced in rats by exercise on a treadmill.

Various regimens of treadmill exercise (0% slope) were used with rats: 60 min at 15 m/min (T-15), 180 min at 10 m/min (T-10), and 60 min/day at 15 m/min for 6 consecutive days (T-15-6). Exercise resulted in 1) decreases in the absolute number of mononuclear spleen cells in T-10 rats, 2) significant increases in in vitro splenic T-cell blastogenesis in response to phytohemagglutinin in T-10 rats, and 3) significant decreases in T-cell blastogenesis in T-15-6 rats. T-15-6 rats were given aminoglutethimide per os before exercise sessions to study the role of corticosteroids in the alteration of splenic T-cell blastogenesis. Aminoglutethimide significantly increased the T-cell blastogenesis in these T-15-6 rats compared with those not given aminoglutethimide, whereas it had no effect on immune parameters of sedentary rats. These results show that immunomodulations in the rat depend on the treadmill exercise regimen employed. If the mechanisms of the immunomodulation induced by isolated exercise of long duration are not elucidated, these data suggest that corticosteroids are involved in the alteration in T-cell blastogenesis induced by chronic muscular exercise.

Aminoglutethimide↗

PubMed1994

Testing of lipoxygenase inhibitors, cyclooxygenase inhibitors, drugs with immunomodulating properties and some reference antipsoriatic drugs in the modified mouse tail test, an animal model of psoriasis.

Topical administration of lipoxygenase and cyclooxygenase inhibitors, antipsoriatic drugs and some immunomodulating drugs on adult mouse tail scales showed variable induction of of orthokeratosis. Dithranol and retinoic acid showed ED50 concentrations of 0.5% and 0.23%, respectively. The lipoxygenase inhibitors catechol and octyl gallate showed ED50 of 2.5 and 13.4%. 10% lonapalene showed 20% activity, curcumin, linoleic acid, primrose oil and AA673 10-15% activity, methyl and ethyl gallate 5% activity, nordihydroguaiaretic acid, diethylcarbamazine, ebselen, esculetin, quercetin, AA861, gallic acid, dodecyl gallate and 15-hydroxyeicosatetraenoic acid no activity. The cyclooxygenase inhibitors indomethacin, acetylsalicylic acid and bufexamac were inactive, benoxaprofen showed 14% activity. The immunomodulating drugs fluorouracil and triamcinolone showed > 10% activity, cyclosporin A and thalidomide no activity. Fumaric acid showed 5% activity. The results show that this model could be proposed for screening antipsoriatic drugs.

Animals↗

PubMed1983

Combination therapy of radiation and immunomodulators in the treatment of MM46 tumor transplanted in C3H/He mice.

Female C3H/He mice aged 10 weeks with transplanted MM46 tumor were used in an investigation of the timing of administration of immunomodulators, such as PSK (a protein-bound polysaccharide prepared from Coriolus versicolor), OK-432 (streptococcal preparation), bestatin (inhibitor of aminopeptidase B) combined with two fractionated local irradiation with the total dose of 3,000 rad. The daily dose of 250 mg/kg of PSK, 1.0 KE/mouse of OK-432, or 300 micrograms/mouse of bestatin were injected intraperitoneally for 4 consecutive days before or after irradiation. The antitumor effect was evaluated by the changes of tumor volume and survival curves. When PSK or OK-432 was administered after irradiation, tumor growth was decreased and 60-day survival rate and survival curve were significantly elongated compared with the control group and the group to which PSK or OK-432 were administered before irradiation (p less than 0.025, p less than 0.05, respectively). As for bestatin, no remarkable difference was observed irrespective of the timing of administration. These results suggested that some immunomodulators show different antitumor activity depending on the combined timing relative to radiotherapy.

Adjuvants, Immunologic↗

PubMed2005

Immunomodulator FTY720 Induces eNOS-dependent arterial vasodilatation via the lysophospholipid receptor S1P3.

The novel immunomodulator FTY720 is effective in experimental models of transplantation and autoimmunity, and is currently undergoing Phase III clinical trials for prevention of kidney graft rejection. FTY720 is a structural analogue of sphingosine-1-phosphate (S1P) and activates several of the S1P receptors. We show that FTY720 induces endothelium-dependent arterial vasodilation in phenylephrine precontracted mouse aortae. Vasodilation did not occur in thoracic aortic rings from eNOS-deficient mice, implicating and effect dependent of activation of the eNOS/NO pathway. Accordingly, FTY720 induced NO release, Akt-dependent eNOS phosphorylation and activation in human endothelial cells. For biological efficacy, FTY720 required endogenous phosphorylation, since addition of the sphingosine kinase antagonist N',N-dimethylsphingosine (DMS) prevented activation of eNOS in vitro and inhibited vasodilation in isolated arteries. The endothelial phosphorylation of FTY720 was extremely rapid with almost complete conversion after 10 minutes as determined by mass spectrometry. Finally, we identified the lysophospholipid receptor S1P3 as the S1P receptor responsible for arterial vasodilation by FTY720, as the effect was completely abolished in arteries from S1P3-deficient mice. In summary, we have identified FTY720 as the first immunomodulator for prevention of organ graft rejection in clinical development that, in addition, positively affects the endothelium by stimulating NO production, and thus potentially displaying beneficial effects on transplant survival beyond classical T cell immunosuppression.

Cells, Cultured↗

PubMedDate not supplied

Cellular and humoral systemic and mucosal immune responses stimulated by an oral polybacterial immunomodulator in patients with chronic urinary tract infections.

An oral polybacterial immunomodulator Urostim (U), composed of killed cells and their lysates from E. coli expressing type 1 and Pili, E. coli Rc mutant, P. mirabilis, K. pneumoniae and E. faecalis was created for immunoprophylaxis and immunotherapy of urinary tract infections (UTIs). In experimental animal models, the stimulating effect of U on lymphocyte functional activity, macrophage phagocytosis and antibody producing cells, was established. In this study the immuno-modulating effects of U on the proliferating capacity and ultrastructural morphologic changes of lymphocytes, cytokine production and specific systemic humoral and mucosal immune responses in patients with UTIs have been evaluated. Patients enrolled in the study, received orally 50 mg U daily for a period of three months. On days 0, 30 and 90 a quantitative analysis was performed on lymphoproliferative responses to polyclonal mitogens, IL-2 and the specific antigen U, the production of specific serum and saliva IgA, IgM and IgG antibodies to all components of U and the concentration of pro-inflammatory cytokines. There was significant improvement of non-specific and specific lymphoproliferative responses on days 30 and 90 after the onset of treatment with U, confirmed by electronmicroscopic studies. The highest concentrations of serum proinflammatory cytokines TNF-alpha, IL-1beta and IL-6 were registered at baseline followed by a decrease until the end of the observation period. This finding correlates with the gradual decrease of immune activation as measured by the spontaneous lymphocyte proliferation. Data from the production of specific antibacterial antibodies in serum and saliva show two types of reactions. The first type was registered in patients with low pre-treatment levels in whom the concentration of specific antibodies increased on days 30 and 90. The second type of reaction was observed in patients with high pre-treatment levels, which dropped on day 30 and were usually followed by an increase at the end of the study. These results provide evidence for the immuno-modulating effect of U. Our data show that the oral administration of the polybacterial immunomodulator Urostim stimulates adequate cellular and humoral systemic and mucosal immune responses in patients with chronic UTIs.

Adjuvants, Immunologic↗

PubMed1996

Introductory remarks: immunosuppressive and immunomodulating drugs, where and how do they act?

Immunotherapies used in multiple sclerosis are reviewed. The mechanisms of action supporting their clinical application are described according to our current understanding. Immune treatments can be divided into three groups: (1) cytostatic and cytotoxic immunosuppressants which block the cell cycle of immunocompetent cells and/or provoke their deletion; (2) immunomodulators which specifically interfere in cellular or humoral immune mechanisms; (3) immunoregulators which restore immunodeficient states but have also immunosuppressive properties at the same time. Numerous attempts have been made to correct almost all abnormal immune mechanisms underlying disease progression. The results of those clinical trials are reviewed. Recent studies have demonstrated that a severe, unspecific and sustained immunosuppression markedly downregulates the clinical and pathological activity of the disease. Unfortunately, serious delayed adverse effects prevent a long-term administration. Recent specific immunomodulators with an acceptable toxicity have provided modest but unquestionable benefit on the attack rate and MRI lesion burden. No clear effect on progression has been demonstrated to date. There is still much work to be done to improve the efficacy of our current therapies on the attack rate and particularly on the progression. Several promising new compounds are already under evaluation. Another approach is combination therapies which will certainly become critical in MS like in other autoimmune diseases.

Adjuvants, Immunologic↗

PubMed2004

Induction of tolerance using Fas ligand: a double-edged immunomodulator.

Apoptosis mediated by Fas ligand (FasL) interaction with Fas receptor plays a pivotal regulatory role in immune homeostasis, immune privilege, and self-tolerance. FasL, therefore, has been extensively exploited as an immunomodulatory agent to induce tolerance to both autoimmune and foreign antigens with conflicting results. Difficulties associated with the use of FasL as a tolerogenic factor may arise from (1) its complex posttranslational regulation, (2) the opposing functions of different forms of FasL, (3) different modes of expression, systemic versus localized and transient versus continuous, (4) the level and duration of expression, (5) the sensitivity of target tissues to Fas/FasL-mediated apoptosis and the efficiency of antigen presentation in these tissues, and (6) the types and levels of cytokines, chemokines, and metalloproteinases in the extracellular milieu of the target tissues. Thus, the effective use of FasL as an immunomodulator to achieve durable antigen-specific immune tolerance requires careful consideration of all of these parameters and the design of treatment regimens that maximize tolerogenic efficacy, while minimizing the non-tolerogenic and toxic functions of this molecule. This review summarizes the current status of FasL as a tolerogenic agent, problems associated with its use as an immunomodulator, and new strategies to improve its therapeutic potential.

Animals↗

PubMed2006

Immunomodulation of transgene responses following naked DNA transfer of human factor VIII into hemophilia A mice.

A robust humoral immune response against human factor VIII (hFVIII) following naked DNA transfer into immunocompetent hemophilia A mice completely inhibits circulating FVIII activity despite initial high-level hFVIII gene expression. To prevent this undesirable response, we compared transient immunomodulation strategies. Eight groups of mice (n = 4-9 per group) were treated with naked DNA transfer of pBS-HCRHPI-hFVIIIA simultaneously with immunosuppressive reagents that included cyclosporine A (CSA), rapamycin (RAP), mycophenylate mofetil (MMF), a combination of CSA and MMF, a combination of RAP and MMF, a monoclonal antibody against murine CD40 ligand (MR1), recombinant murine Ctla4Ig, and a combination of MR1 and Ctla4Ig. All animals except those receiving only CSA exhibited delayed or absent immune responses against hFVIII. The most effective immunosuppressive regimen, the combination of Ctla4Ig and MR1, prevented inhibitor formation in 8 of 9 animals; the ninth had transient low-titer antibodies. All 9 mice of this group produced persistent, therapeutic levels of hFVIII for more than 6 months. When challenged with the T-dependent antigen bacteriophage Phix174, tolerized mice exhibited normal primary and secondary antibody responses, suggesting that transient immunomodulation to disrupt B/T-cell interaction at the time of plasmid injection effectively promoted long-term immune tolerance specific for hFVIII.

Abatacept↗

PubMed1988

Influence of dose and duration of infusion of interleukin-2 on toxicity and immunomodulation.

The purpose of this study was to investigate the effect of dose and duration of infusion of recombinant interleukin-2 (IL-2) on toxicity and immunomodulation. In a phase I/II study, IL-2 was administered intravenously (IV) daily for five consecutive days every other week for 4 weeks of treatment to 23 patients with progressive melanoma, renal, colon, or ovarian cancer by one of four regimens: groups I and II received 3 X 10(5) U/m2/d by two-hour or 24-hour infusion, respectively; groups III and IV received 3 X 10(6) U/m2/d by two-hour or 24-hour infusion, respectively. In a subsequent study, six patients (group V) received a single priming cycle of daily IL-2 for five days at 3 X 10(6) U/m2/d in divided 15-minute infusions every eight hours, before undergoing leukapheresis for lymphokine-activated killer (LAK) cell generation. Toxicity was mild with 3 X 10(5) U/m2/d, but severe chills and fever, moderate hypotension (not requiring IV pressors), and weight gain were observed with 3 X 10(6) U/m2/d. Toxicity was also related to the duration of infusion. In group IV (continuous infusion), fluid retention, weight gain, and azotemia were more frequent and severe than in groups III or V, in which the same total dose was administered by two-hour infusion or in three divided 15-minute infusions. IL-2 induced rebound lymphocytosis, which was directly dose-related and significantly higher in group IV (continuous infusion) than in groups III or V. Dramatic increases in the percentage and absolute number of cells expressing the IL-2 receptor were also most pronounced in group IV. With the higher dose of IL-2, LAK cells appeared in the circulation, and natural killer (NK) cytotoxicity was augmented. The results showed that the toxicity and immunomodulation by IL-2 are dose-dependent and are maximal by continuous infusion compared with two-hour or divided every eight hours infusions.

Adult↗

PubMed1984

Immunomodulation of relapsing experimental allergic encephalomyelitis.

Mice immunized to produce relapsing experimental allergic encephalomyelitis (R-EAE) were treated with immunomodulating agents known to affect acute monophasic experimental allergic encephalomyelitis. Pretreatment with either mouse spinal cord or myelin basic protein in incomplete Freund's adjuvant decreased the incidence of R-EAE from 77% to 28 and 31%, respectively. Single doses of cyclophosphamide (CY) at the time of immunization did not affect development of R-EAE. CY given repetitively in low doses decreased the incidence of R-EAE to 10%. Therefore, R-EAE can be altered by immunomodulation, but the patterns differ from those seen in acute EAE.

Animals↗

PubMed2002

Statins as immunomodulators: comparison with interferon-beta 1b in MS.

BACKGROUND: Recent data suggest that statins may be potent immunomodulatory agents. In order to evaluate the potential role of statins as immunomodulators in MS, the authors studied their immunologic effects in vitro and compared them to interferon (IFN)beta-1b. METHODS: Peripheral blood mononuclear cells (PBMC) obtained from untreated or IFN beta-1-treated patients with relapsing-remitting MS or from healthy donors (HD) and T cells were stimulated with concanavalin A, phytohemagglutinin, or antibody to CD3 in the presence of lovastatin, simvastatin, mevastatin, IFN beta-1b, or statins plus IFN beta-1b. The authors analyzed proliferative activity of T cells and B cells, cytokine production and release, activity of matrix metalloproteinases (MMP), and surface expression of activation markers, adhesion molecules, and chemokine receptors on both T and B cells. RESULTS: All three statins inhibited proliferation of stimulated PBMC in a dose-dependent manner, with simvastatin being the most potent, followed by lovastatin and mevastatin. IFN beta-1b showed a similar effect; statins and IFN beta-1b together added their inhibitory potentials. Furthermore, statins reduced the expression of activation-induced adhesion molecules on T cells, modified the T helper 1/T helper 2 cytokine balance, reduced MMP-9, and downregulated chemokine receptors on both B and T cells. Besides strong anti-inflammatory properties, statins also exhibited some proinflammatory effects. CONCLUSIONS: Statins are effective immunomodulators in vitro that merit evaluation as treatment for MS.

Adjuvants, Immunologic↗

PubMed2006

The use of immunomodulators as an adjunct to antituberculous chemotherapy in non-responsive patients with osteo-articular tuberculosis.

We studied 51 patients with osteo-articular tuberculosis who were divided into two groups. Group I comprised 31 newly-diagnosed patients who were given first-line antituberculous treatment consisting of isoniazid, rifampicin, ethambutol and pyrazinamide. Group II (non-responders) consisted of 20 patients with a history of clinical non-responsiveness to supervised uninterrupted antituberculous treatment for a minimum of three months or a recurrence of a previous lesion which on clinical observation had healed. No patient in either group was HIV-positive. Group II were treated with an immunomodulation regime of intradermal BCG, oral levamisole and intramuscular diphtheria and tetanus vaccines as an adjunct for eight weeks in addition to antituberculous treatment. We gave antituberculous treatment for a total of 12 to 18 months in both groups and they were followed up for a mean of 30.2 months (24 to 49). A series of 20 healthy blood donors served as a control group.Twenty-nine (93.6%) of the 31 patients in group I and 14 of the 20 (70%) in group II had a clinicoradiological healing response to treatment by five months. The CD4 cell count in both groups was depressed at the time of enrolment, with a greater degree of depression in the group-II patients (686 cells/mm(3) (sd 261) and 545 cells/mm(3) (sd 137), respectively; p < 0.05). After treatment for three months both groups showed significant elevation of the CD4 cell count, reaching a level comparable with the control group. However, the mean CD4 cell count of group II (945 cells/mm(3) (sd 343)) still remained lower than that of group I (1071 cells/mm(3) (sd 290)), but the difference was not significant. Our study has shown encouraging results after immunomodulation and antituberculous treatment in non-responsive patients. The pattern of change in the CD4 cell count in response to treatment may be a reliable clinical indicator.

Adjuvants, Immunologic↗

PubMedDate not supplied

Immunomodulating polysaccharide fractions of Menyanthes trifoliata L.

Looking for new plant sources of immunomodulating agents polysaccharide-rich fractions (PS) from Menyanthes trifoliata L. (Menyanthaceae) have been isolated. The herb of Menyanthes trifoliata L. was sequentially extracted with water, 0.1 M NaOH, 8% CH3COOH, and 1 M NaOH. After dialysis and resolution on Biogel P-10 four homogenic (B-4, B-5, C-4, D-5) and two nonhomogenic (A-3 and D-4) PS were isolated. About 0.5% of PS over 3500 Da were found in the dry plant material. They were characterized through chemical analysis, NMR and vibrational spectroscopy. Speciation analysis of chosen metal/metaloid elements was performed and an exceptionally high concentration of Se was found in PS of a pure water extract (A-3). The biological tests on the immunomodulating influence with human blood-derived lymphocytes and granulocytes revealed that two fractions, B-4 and B-5, were strong stimulators of immune cells, whereas fractions D-5 and A-3 were found as potent suppressive and anti-inflammatory agents. The applied isolation procedures led to the separation of active compounds into stimulatory and inhibitory fractions.

Asteraceae↗

PubMed2002

Immunomodulation with antibodies: clinical application in ovarian cancer and other malignancies.

This review identifies the role of antibodies in the field of therapeutic cancer vaccines. Ovarian cancer is used as a model to review advances in therapeutic vaccine development with a focus on antibodies as immunomodulators and antigen mimetics, highlighting research on B43.13 and ACA125. The interaction of biological immunomodulation and chemotherapy is discussed. Requirements of antigen processing and recent advances in the field of dendritic cell biology are critical to current understanding of potent immune response induction. Future directions including use of growth factors, adjuvants and cellular therapies to enhance effects may potentiate observed effects and provide clues for application in many cancers and beyond oncology.

Animals↗

PubMed2006

Immunomodulating effect of vitamin D3 derivatives on type-1 cellular immunity.

1 alpha,25-dihydroxyvitamin D3 [Calcitriol or 1,25(OH)(2)D(3)] is an important active metabolite involved in multiple functions but its calcemic effect in vivo limits its therapeutic applications. On the other hand, 22-oxa-1 alpha,25-dihydroxyvitamin D(3) (22-oxacalcitriol or 22-Oxa-1 alpha,25-D(3)), a low calcemic analog of vitamin D3 (VitD3), has been widely used as a drug for the secondary hyperparathyroidism. Here, we investigated immunomodulating effect of these two VitD3 derivatives on the differentiation of type-1 immunoregulatory cells such as dendritic cells (DC1), cytotoxic T cells (Tc1) and helper T cells (Th1). BALB/c mouse bone marrow-derived DC (BMDC1) induced by culture with Th1 condition (GM-CSF, IL-3, IL-12 and IFN-gamma) expressed higher levels of MHC Class I and Class II molecules and co-stimulatory molecules compared with BMDC0 induced by neutral condition (GM-CSF+IL-3). In addition, BMDC1 showed stronger immunostimulating activity to induce alloantigen (H-2(d))-specific cytotoxic T lymphocytes (CTL) compared with BMDC0. However, if VitD3 derivatives were added into the culture for BMDC1 induction, the expression of functional molecules and type-1 IFNs were greatly inhibited. Moreover, VitD3 derivative-treated BMDC1 lost their immunostimulating activity to induce alloantigen-specific IFN-gamma-producing Tc1. In addition, it was demonstrated that the addition of VitD3 derivatives inhibited the differentiation of IFN-gamma-producing Th1 cells from ovalbumin (OVA)-specific naive Th cells, while it rather augmented the differentiation of IL-4- or IL-10-producing Th2 cells. There was no significant difference in immunomodulating activity between 1,25(OH)(2)D(3) and 22-Oxa-1 alpha,25-D(3). Thus, VitD3 derivatives are demonstrated to inhibit the functional differentiation of DC1, Tc1 and Th1 cells, which play a critical role in type-1 cellular immune responses.

Animals↗