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At least 451 records · Page 25Linked to original sources
PubMed2004

Prophylaxis of autoimmune diabetes by antigen based immune modulation: are we there yet?

Autoimmune type 1 diabetes (early onset/juvenile and slow onset T1D) is a disease mediated by autoreactive T cells accompanied by autoantibodies against islet associated antigens. The genetic predisposition, the association with certain HLA alleles (DR4 and DQ8) as well as the possibility to identify high-risk subjects by autoantibody measurement, fueled hope in regards to potential prophylaxis by vaccination. Numerous preclinical studies along with accumulating evidence for the role of certain autoantigens and putative dominant epitopes created the premises of clinical trials addressing this objective. However, the disappointing outcomes of many of such trials made it clear that significant challenges to clinical application of this concept must be addressed: we do not know at this point, how to choose the most appropriate set of autoantigens, how to optimally use them as a vaccine, whether to define and enroll only a subset of recipients, how to monitor their T cell responses to the vaccine and lastly, which the end-points of clinical T1D trials from an immunologic or metabolic perspective should be? Herein, we will approach some of the opportunities and obstacles associated with this intriguing strategy to fight autoimmune diabetes based on promising novel insight gained form studies with animal models.

Autoantigens↗
PubMed2005

[CD4+CD25+ T regulatory cells: their physiology and role in modulating immune response].

Understanding the role of immune system homeostatic balance is crucial for a better understanding of the pathogenesis of many diseases. The efficient regulation of immune response has been recently investigated in numerous studies that emphasize the important role of CD4+CD25+ regulatory T cells. These regulatory cells suppress the proliferation and cytokine secretion of effector cells directly via cell-cell contact and probably indirectly via TGF-beta. This makes T regulatory cells responsible for the control and suppression of inappropriate immune response to self antigens. Moreover, CD4+CD25+ regulatory T cells have an important function in the immunopathology of cancer, allotransplantion, and allergy. Based on murine and human studies, this review presents a characterization of the origin, phenotype, and function of CD4+CD25+ regulatory T cells. In addition, we show a hypothetical mode of the in vivo action of regulatory T cells, which play a central role in maintaining immune homeostasis.

Animals↗
PubMed1991

Replication-defective viruses modulate immune responses.

By immunizing inbred mice with purified replication-competent, defective virus particles, or an admixture of the two, differential effects on the cellular immune system have been uncovered. Defective virus, exemplified by the vesicular stomatitis virus (VSV) defective interfering particle (DI 0.33), induced in BALB/c mice low levels of proliferating, IL-2 secreting, and cytolytic Ag-specific T lymphocytes. This was not caused by a dominant suppressor cell response, or by a failure to stimulate lymphokine-secreting cells, but appeared to reflect a reduced efficiency of priming as compared with standard virus. Mice primed with a mixture of wt and DI virus showed reduced proliferation compared with mice primed with wt virus. When histocompatible target cells were sensitized by pure DI particles, they were neither recognized nor lysed by CD8+ CTL. Cells co-infected with wt and DI particles were not as readily lysed by CD8+ CTL as cells infected by VSV alone. The extent of this reduction was dependent on the concentration of DI particles. This suggests that DI particles may have prevented the proper presentation of endogenously synthesized Ag for recognition by CD8+ CTL. Metabolic labeling studies indicated that the presence of DI particles suppressed the synthesis of viral proteins in dually infected cells. However, CD4+ T lymphocyte clones recognized and efficiently lysed histocompatible Ia+ cells infected with DI particles alone or co-infected with replication-competent and defective virus.

Animals↗
PubMed2006

Local immune modulator (imiquimod 5% cream) as adjuvant treatment after incomplete Mohs micrographic surgery for large, mixed type basal cell carcinoma: a report of 3 cases.

BACKGROUND: Surgical excision, including Mohs micrographic surgery, is the treatment of first choice for basal cell carcinoma (BCC). Occasionally, the Mohs procedure has to be ceased prematurely for unforeseen reasons. OBJECTIVE: We sought for possibilities to adjuvantly treat patients in which superficial basal cell carcinoma remained after incomplete Mohs surgery. METHODS: We report 3 cases of patients in which Mohs micrographic surgery for their large basal cell carcinomas was ceased for different unforeseen reasons, with remaining superficial fields of BCC after the aggressive and deeply localized part had been removed. Three weeks after closure of the defect, adjuvant therapy for the superficial remnants of the tumor with imiquimod 5% cream was given for 6 weeks, covering at least 1 centimeter around the surgically treated area. RESULTS: The treatment was well accepted with no serious side effects and a good cosmetic result. No recurrences were seen after a follow-up period of 20 to 34 months. CONCLUSION: A combination of surgical intervention for the central deeper part of the BCC and topical imiquimod 5% cream for the superficial part at the border might be a therapeutic option for those patients with multiple facial BCCs, severe sun damage, and extensive surgery in the past, in whom completion of the Mohs surgical procedure for the entire tumor is not possible for different reasons.

Administration, Topical↗
PubMed1990

[Immune modulating effect of isoprinosine in patients with post-alcoholic liver cirrhosis].

Immunomodulating effect of isoprinosine was estimated in group of 10 patients with postalcoholic liver cirrhosis and compared with another group of 10 patients with postinflammatory liver cirrhosis with infection of hepatitis B virus. Disturbances of immunologic reactivity in the patients with postalcoholic liver cirrhosis mainly concerned increased immunoglobulin G, A concentrations in the blood serum, decreased percentage values of lymphocytes T and their subpopulations (lymphocytes T4 and T8) and increased percentage of lymphocytes B. Disturbances of the examined indices of the immunologic reactivity in the group of patient with postinflammatory liver cirrhosis concerned increased concentrations of circulating immunologic complexes, immunoglobulins A and M in the blood serum and decreased percentage of lymphocytes T and their subpopulation. Treatment with isoprinosine resulted in different immunologic effect in the examined patients concerning mainly increased concentrations of circulating immunologic complexes in the blood serum and increased percentage values of lymphocytes T, T4, T8, B in the course of postalcoholic liver cirrhosis. Patients with postinflammatory liver cirrhosis treated with isoprinosine mainly showed decreased concentrations of circulating immunologic complexes, immunoglobulins A, M the blood serum, increased percentage values of lymphocytes T4 and T8.

Adult↗
PubMed1991

[Locoregional ascites therapy with cytostatic drugs and immune modulators in gynecologic neoplasms].

35 ovarian cancer patients with ascites have been treated intraperitoneally with mitomycin C or mitoxantrone or interferon beta or tumor necrosis factor (TNF). We observed nor or a little bit ascites in 87.5 per cent after TNF and in 66.5 per cent after mitoxantrone. In addition we applied a systemic monochemotherapy. After mitomycin C or interferon beta only in 40 per cent each an effect could be observed. TNF to day is the most effective substance for treating ascites with moderate toxicity.

Ascites↗
PubMed1991

Biologic and immune modulating agents in the treatment of childhood brain tumors.

The data on the utility of biologic response modifiers are quite sketchy. Although no true home-runs have been hit, there is evidence that some patients will benefit from these immunologic agents. The majority of studies for central nervous system tumors have been done in adults with highly aggressive anaplastic gliomas. Many of these patients had extensive disease at the time of treatment and determination of benefit is difficult. Few pediatric trials have been attempted. The evidence for efficacy for most agents is lacking, although there are encouraging responses in children with isolated leptomeningeal spread to radiolabeled monoclonal antibodies and for patients with progressive intracranial mass lesions to one form of beta-interferon. Given the limited alternatives for many of these patients, and the neurotoxicity of other means of therapy, future studies are clearly indicated in children with malignant brain tumors. The lack of evidence of efficacy in adult glioblastoma trials cannot be used as direct evidence for the nonutility of these agents for childhood brain tumors. By and large, children tend to tolerate higher doses of biologic response modifiers than adults, again raising the hope of greater utility of these drugs for pediatric patients. From the information available, it seems unlikely that these immunomodulating agents, in themselves, will be effective in the treatment of the majority of patients with brain tumors. But in combination with aggressive surgery, radiation, and possibly chemotherapy, these agents may in time add to the armamentarium available for the treatment of childhood brain tumors.

Adjuvants, Immunologic↗
PubMed1978

Pharmacological control of the hormonally modulated immune response. II. Blockade of antibody production by a combination of drugs acting on neuroendocrine functions. Its prevention by gonadotropins and corticotrophin.

Injection of a combination of three drugs, 5-hydroxytryptophan, the alpha-blocker phentolamine and the neuroleptic drug haloperidol into mice before or together with sheep red blood cells (SRBC) induces a complete and long-lasting inhibition of antibody production to SRBC and leads to specific unresponsiveness. The mice unresponsive to SRBC respond normally to another antigen. Treatment with a combination of luteotropic (LH), follicle stimulating (FSH) and corticotropic hormone (ACTH) before administration of drugs and antigen prevents the immune blockade. Injection of SRBC induces an early elevation of LH in blood. This effect is prevented by previous administration of the three drugs in combination. The hormonal response to a second injection of the same antigen of mice previously made 'unresponsive' is different from that of immunized animals. The suppression of these hormonal changes which follow antigen injection by drugs acting on neuroendocrine regulation and cell membrane adrenergic receptors represents a step forward in efforts aimed at a pharmacological control of acquired immunity.

5-Hydroxytryptophan↗
PubMed1989

[Immune modulators in the treatment of malignant melanoma].

The experience gained to date with immunomodulators used as therapeutical and adjuvant measures in the treatment of cutaneous malignant melanoma is reviewed. In large studies no therapeutic effect has been shown for levamisole, DNCB and BCG preparations. The effectiveness of monoclonal antibodies, histamine type 2 receptor antagonists, thymus factors and mistletoe extracts cannot yet be assessed due to a lack of clinical studies. The recent use of the lymphokines: tumor-necrosis factor, interleukin 2 and interferons, has shown that tumor therapy with immunomodulators is possible, but many questions still remain to be answered, so that their use, especially as an adjuvant measure, should be restricted to controlled studies.

Adjuvants, Immunologic↗
PubMed1978

Pharmacologic control of the hormonally modulated immune response. III. Prolongation of allogeneic skin graft rejection and prevention of runt disease by a combination of drugs acting on neuroendocrine functions.

A recently developed pharmacologic means for suppressing acquired immunity by drugs acting on neuroendocrine regulation has been applied to transplantation immune reactions. A number of drugs have been tested singly and in combination for their capacity to suppress the immune response of mice grafted with allogeneic skin. Another model involved newborn F1 hybrid recipients inoculated with spleen cells from donors of parental strains that had been made specifically "unresponsive" by drug and alloantigen treatment. These procedures led to the identification of a combination of four drugs that induced a remarkable delay in allograft rejection and a prolonged unresponsiveness to alloantigens. This combination of drugs also abrogated the graft-vs-host-runting syndrome in newborn hybrid recipients.

Animals↗
PubMed1989

Human platelets involvement in immune modulation of graft rejection in mice.

A cell lysate consisting of human thrombocytes is able after a unique i.p. application in mice to prolonge significantly the survival time of skin allografts. A linear relation is existing between the dosis and the effect within a defined dosis area (100 to 300 x 10(6) Gpt). The correlation was proved by the application of cell lysates from 12 single donors (r = 0.575, P less than 0.05) as well as by the application of 5 differently diluted preparations produced from a concentrated total pool (r = 0.577). The fact is discussed that the protective clinical transplant effects occurring by pre-operatively administered blood transfusions may be due to the same principle of action.

Animals↗