PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Immune suppression”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed2006

Immune suppression of challenged vaccinates as a rigorous assessment of sterile protection by lentiviral vaccines.

We previously reported that an experimental live-attenuated equine infectious anemia virus (EIAV) vaccine, containing a mutated S2 accessory gene, provided protection from disease and detectable infection after virulent virus (EIAV(PV)) challenge [Li F, Craigo JK, Howe L, Steckbeck JD, Cook S, Issel C, et al. A live-attenuated equine infectious anemia virus proviral vaccine with a modified S2 gene provides protection from detectable infection by intravenous virulent virus challenge of experimentally inoculated horses. J Virol 2003;77(13):7244-53; Craigo JK, Li F, Steckbeck JD, Durkin S, Howe L, Cook SJ, et al. Discerning an effective balance between equine infectious anemia virus attenuation and vaccine efficacy. J Virol 2005;79(5):2666-77]. To determine if attenuated EIAV vaccines actually prevent persistent infection by challenge virus, we employed a 14-day dexamethasone treatment of vaccinated horses post-challenge to suppress host immunity and amplify replication levels of any infecting EIAV. At 2 months post-challenge the horses were all protected from virulent-virus challenge, evidenced by a lack of EIA signs and detectable challenge plasma viral RNA. Upon immune suppression, 6/12 horses displayed clinical EIA. Post-immune suppression characterizations demonstrated that the attenuated vaccine evidently prevented detectable challenge virus infection in 50% of horses. These data highlight the utility of post-challenge immune suppression for evaluating persistent viral vaccine protective efficacy.

Adjuvants, Immunologic↗
PubMed1976

Genetic control of specific immune suppression. III. Mapping of H-2 complex complementing genes controlling immune suppression by the random copolymer L-glutamic acid50-L-tyrosine50 (GT).

Earlier studies from our laboratory demonstrated that the terpolymer of L-glutamic acid, L-alanine, and L-tyrpsine (GAT) stimulated the development of T cells capable of specifically suppressing the antibody responses in vivo and in vitro of nonresponder strains (bearing the H-2(s), H-2(q), and H-2(p) haplotypes) to GAT complexed with an immunogenic carrier, methylated bovine serum albumin, MBSA (1,2). We then extended these findings to another antigen, the copolymer of L-glutamic acid and L-tyrosine (GT). None of 19 inbred or congenic resistant mouse strains developed antibody responses to GT after immunization with this synthetic polypeptide in adjuvants. All the strains investigated, however, developed IgG plaque-forming cells (PFC) primary responses to GT complexed with MBSA (3). This permitted us to determine that: (a) preimmunization with GT suppressed the response to GT-MBSA in certain but not in all strains; (b) the suppression could be transferred by thymocytes and spleen cells from GT-primed animals; (c) the development of GT-specific suppressor cells is under dominant control of H-2- linked gene(s) which have been designated specific immune suppressor genes (Is genes); (d) the Is genes are antigen specific since GAT-MBSA responses are suppressed by GAT in strains carrying the H-2(q) haplotype, while GT-MBSA responses are not suppressed by the related polymer GT in these same strains (3,4). The experiments reported in this study map the Is genes responsible for GT-specific suppression within the H-2 complex. The data indicate that the K and D loci are not concerned with GT-specific suppression, and that this phenomenon is controlled by complementing or interacting genes which map on either side of cross-over events between the IB and IC subregions.

Animals↗
PubMed1996

Update on the mechanisms of immune suppression of injury and immune modulation.

Major trauma results in massive impairment of immunologic reactivity, the clinical consequence of which consists in the high susceptibility of the traumatized individual toward serious infection. Whereas parts of the immune system are stimulated within a systemic, nondiscriminant, excessive whole-body inflammation, other functions within the complex of cell-mediated immunity (CMI) are dramatically paralyzed. Immune abnormalities in the aftermath of trauma occur in a sequence of states of cellular activation and within a complex order of events that is not yet well understood. Traumatic stress is causing disintegration of the intact monocyte (Mphi)-T cell interaction, which is associated with profound changes in Mphi forward-regulatory capacities and substantial depression of T cell function. Extensive tissue destruction results in the generation of numerous stimuli, such as phagocytosis, immune complexes, complement split products, and endo- and exotoxins, all of which contribute to excessive Mphi activation. Mphi then rapidly produce and release prostaglandin E2 (PGE2), a powerful endogenous immune suppressant. PGE2 is an inhibitor of T cell mitogenesis, interleukin 2 (IL-2) production, and IL-2 receptor expression; and it has a massive impact on the quality of B cell antibody synthesis. Most importantly, PGE2 represents an important cofactor for the induction of T-helper lymphocyte (TH) activity toward the TH2 direction. TH2 cells are associated with the synthesis of immunosuppressive cytokines, such as IL-4 and IL-10. Although immunosuppressive substrates are inhibitory for TH1 cells-the functional carriers of CMI-they support TH2 activity, which predisposes the host to develop infection. The endogenous ability of the organism to survive overwhelming trauma is insufficient and requires major exogenous support. Immune modulatory interventions, depending on the immune abnormalities seen in the traumatized host, should be started as early as possible after trauma in a preventive fashion to protect against organ tissue destruction. Ideally, it should protect all cellular host defense compartments from hyperactivation as well as from exhaustion. We do believe that only a combination of drugs can effectively control the posttraumatic dyshomeostasis of the various cell systems.

Adjuvants, Immunologic↗
PubMed1990

HLA-linked immune suppression genes.

Genetic control of immune response was investigated by family and population analyses in humans. It was first recognized that there are high responders and low or non responders to natural antigens in human population. Family analysis revealed that low responsiveness to streptococcal cell wall antigen (SCW) was inherited as an HLA-linked dominant trait. CD8+ suppressor T cells existed in low responders and depletion of the CD8+ T cells from low responders could restore the strong immune response to SCW. Therefore the gene controlling the low response to SCW was designated as an immune suppression gene for SCW. Immune suppression gene for SCW was in strong linkage disequilibrium with particular alleles of HLA-DQ locus. The association between HLA-DQ alleles and low responsiveness mediated by CD8+ suppressor T cell was also observed for schistosomal antigen, Mycobacterium leprae antigen, tetanus toxoid, cryptomeria pollen antigen and hepatitis B virus surface antigen suggesting that low responsiveness to those antigens was also controlled by immune suppression genes. Anti-HLA-DR monoclonal antibodies inhibited the immune response to those antigens of high responders in vitro, but anti-HLA-DQ monoclonal antibodies did not. On the other hand, anti-HLA-DQ monoclonal antibodies restored the immune response in low responders. Therefore, it is suggested that HLA-DR upregulates immune response and that HLA-DQ downregulates it and that HLA-DQ is epistatic to HLA-DR in the regulation of immune response in humans. Furthermore, direct evidence for the differential in immune regulation between HLA-DR and DQ was obtained by analyzing the SCW specific T cell lines from low responders. SCW specific and HLA-DQ restricted CD4+ T cell lines could activate CD8+ suppressor T cells which in turn downregulate SCW specific CD4+ T cells whereas SCW specific and HLA-DR restricted CD4+ T cell lines could not activate CD8+ suppressor T cells. All these observation clearly demonstrated that the HLA-linked immune suppression genes exist in humans to control low response to natural antigens.

Animals↗
PubMed2000

Reversal of ultraviolet radiation-induced immune suppression by recombinant interleukin-12: suppression of cytokine production.

Exposure to ultraviolet (UV) radiation, a complete carcinogen, suppresses the immune response. Data from a number of laboratories have indicated that one consequence of UV exposure is suppressed T helper type 1 (Th1) cell function with normal Th2 cell activation, resulting in a shift to a Th2-like phenotype. The reversal of UV-induced immune suppression and tolerance induction by recombinant interleukin-12 (rIL-12) supports this observation. The focus of this study was to determine the mechanism(s) by which rIL-12 reverses UV-induced immune suppression. Two possibilities were considered: up-regulation of interferon-gamma (IFN-gamma) secretion by rIL-12 and suppression of UV-induced cytokine secretion by rIL-12. To our surprise we found that the ability of rIL-12 to overcome UV-induced immune suppression was independent of its ability to up-regulate IFN-gamma secretion. Rather, rIL-12 suppressed the production of cytokines that are known to be important in UV-induced immune suppression. Injecting UV-irradiated mice with rIL-12, or adding rIL-12 to UV-irradiated keratinocyte cultures suppressed IL-10 secretion, in part by affecting the transcription of the IL-10 gene. Furthermore, we found that rIL-12 suppressed UV-induced tumour necrosis factor-alpha (TNF-alpha) production. Because IL-10 is involved in the UV-induced suppression of delayed-type hypersensitivity and TNF-alpha in the UV-induced suppression of contact allergy, these findings provide a mechanism to explain how rIL-12 overcomes UV-induced immune suppression in these related but different immune reactions. In addition, they suggest a novel mechanism by which rIL-12 alters immune reactivity, direct suppression of cytokine secretion induced by UV radiation.

Animals↗
PubMed1996

Immune suppressive virus-like particles in a Drosophila parasitoid: significance of their intraspecific morphological variations.

The Eucoilid parasitoid Leptopilina boulardi is able to suppress its host Drosophila melanogaster immune reaction. Some strains, however, are non-immune suppressive to that host. Virus-like particles (VLPs) responsible for the immune suppressive ability were investigated in different strains of L. boulardi with histochemical and ultrastructural techniques. Membrane-bound particles containing vesicles were observed in the reservoir of the long gland and also in the egg canal of the ovipositor. These particles are homologous with the immune suppressive VLPs already described in the reservoir of L. heterotoma. Similarities were also observed with the L2 particles described previously around the chorion of the parasitoid egg after infestation. A weak positive DNA specific histochemical reaction was observed inside the reservoir and at the ultrastructural level. Feulgen-derived techniques demonstrated that the reaction was localized inside the particles. The morphology of the particles as well as the immune suppressive ability varied between strains. Two morphotypes of VLPs are described; the 'Is' morphotype (always observed in immune suppressive or Is strains) and the 'NIs' morphotype (observed in the non-immune suppressive or NIs strain). The hybrids between Is and NIs strains produce a third type of particle, the 'HIs' morphotype with half-immune suppressive ability and intermediate morphology. The origin of the particles' immune suppressive activity against D. melanogaster is discussed within the scope of host specificity.

Animals↗
PubMed2005

Immune suppression in cancer: effects on immune cells, mechanisms and future therapeutic intervention.

Evidence indicates that the healthy immune system is necessary for control of malignant disease and that immune suppression associated with cancer contributes to its progression. Tumors have developed strategies to successfully evade the host immune system, and various molecular and cellular mechanisms responsible for tumor evasion have been identified. Certain of these mechanisms target immune anti-tumor effector cells. Dysfunction and apoptosis of these cells in the tumor-bearing host creates an immune imbalance that cannot be corrected by immunotherapies aimed only at activation of anti-tumor immune responses. Reversal of existing immune dysfunction(s) and normalization of lymphocyte homeostasis in patients with cancer needs to be a part of future cancer immunotherapy. Therapeutic strategies are being designed to correct the immune imbalance, deliver adequate in vivo stimulation, transfer effector T cells capable of in vivo expansion and provide protection for the immune effector cells re-populating the host. Survival of these cells and long-term memory development in patients with malignancy are necessary for improving clinical benefits of cancer immunotherapies.

Humans↗
PubMed2000

The role of cytokines in UV-induced systemic immune suppression.

Exposure to ultraviolet radiation induces skin cancer. In addition, UV exposure suppresses the immune response. The mechanism by which skin exposure to UV induces systemic immune suppression is not entirely clear, but a role for cytokines secreted by irradiated epidermal cells has been described. Ultimately, these immune regulatory cytokines affect antigen presenting cell function at distant sites. We describe here preliminary findings suggesting that one consequence of UV exposure is an alteration of IL-12 production by lymph node dendritic cells that result in impaired immune function.

Animals↗
PubMed1975

Influence of antibody-mediated immune suppression on clinical, viral, and immune responses to swine influenza infection.

Antibody-mediated immune suppression occurred when newborn pigs with naturally acquired passive antibody were exposed to seine influenza virus. Frequency and relative ease of recovery of virus from nasal secretions were inversely related to the concentration of specific passive antibody existing at time of exposure. Severe overt respiratory signs during the acute stages of the disease were observed only in pigs with low passive antibody concentrations. The concentration of passive antibody at the time of exposure determined the immune status of the pig during the convalescent stage of disease. Infection could occur in the presence of high passive antibody concentrations, but the pig was not immunologically stimulated. Reexposure after the decay of passive antibody produced primary immune respone, severe clinical reinfection, and recovery of virus from nasal secretions for a period of time similar to that seen in pigs having their first exposure. Infection of newborn pigs with low passive antibody concentrations led to immunologic priming. A second exposure to virus produced a secondary immune response, mild clinical disease, and shortened time during which virus was recovered from nasal secretions. The relevance of these studies for the practice of vaccination or infections of the dam before parturition so that the neonate will have specific passive immunity is discussed.

Aerosols↗
PubMed2000

The effect of a vitamin A acetate diet on ultraviolet radiation-induced immune suppression as measured by contact hypersensitivity in mice.

The adverse health effects caused by increased exposure to ultraviolet radiation (UVR) due to deterioration of stratospheric ozone are of major concern. These health effects include sunburn, skin cancer, cataracts and immune suppression. Immune suppression has been associated with the release of cytokines, a defect in antigen presentation, induction of suppressor T cells and suppression of contact hypersensitivity (CH). CH is typically assessed by the mouse ear swelling test (MEST). Previous studies have demonstrated enhanced CH responses with vitamin A acetate (VAA) dietary supplementation assessed by MEST and the local lymph node assay (LLNA). To determine the effect that VAA has on UVR-induced immune suppression, we examined both the induction and elicitation phases of CH using murine models. The MEST was used to evaluate the interaction of UVR and VAA on CH elicitation. However, a positive MEST response requires that the induction phase as well as the elicitation phase of CH be functional. The LLNA was used to evaluate the interaction of UVR and VAA only on CH induction. We tested the hypothesis that mice maintained on a VAA-enriched diet are more resistant to UVR-induced immune suppression (CH) than those maintained on a control diet. Mice were maintained on a VAA-enriched or the control diet for 3 weeks and then exposed to UVR 3 days prior to sensitization with 2,4-dinitrofluorobenzene (DNFB). VAA enhanced the MEST response in both UVR-exposed and non-UVR-exposed mice. The VAA-enriched diet did not significantly alter the LLNA response in either UVR- or non-UVR-exposed mice. However, there was significant suppression in CH by UVR as measured by the LLNA. These results indicate that (1) the VAA-enriched diet does not restore the number of proliferating cells in the CH induction phase of UVR-induced immunosuppression; (2) the immunosuppressive effects of UVR affect the induction phase of CH; and (3) the LLNA should be examined as an alternative to the MEST for measurement of UVR-induced immunosuppression. The data indicate that the VAA-enriched diet enhanced the elicitation response (MEST) but not the earlier induction phase (LLNA). Further studies are necessary to define mechanisms of action, but modulation of cytokines and effects of specific lymphocyte subsets, as well as systemic effects and local modulation at the site of elicitation are possible. Additionally, future studies to evaluate the effect of the VAA-enriched diet when multiple doses of both UVR and DNFB are used would be of interest for both the LLNA and MEST end-points.

Animals↗
PubMed1993

Polychlorinated biphenyl-induced immune suppression: castration, but not adrenalectomy or RU 38486 treatment, partially restores the suppressed cytotoxic T lymphocyte response to alloantigen.

The cytotoxic T lymphocyte (CTL) response to allogeneic P815 tumor in C57bl/6 mice is dose-dependently suppressed after treatment with 3,3',4,4',5,5'-hexachlorobiphenyl (HxCB). Elevation of plasma corticosterone (CS) is also observed coincident with CTL suppression. Because immune suppression is inducible by glucocorticoid administration, the role of elevated CS was investigated as an indirect mechanism of HxCB-induced immunotoxicity. In multiple experiments, HxCB treatment (10 mg/kg b.w.) consistently reduced CTL activity by 70 to 85% in male mice. Adrenalectomy failed to alter the suppression of CTL activity by HxCB. However, the mortality rate was high (> or = 70%) in these experiments and plasma CS elevation persisted in HxCB-treated adrenalectomy survivors. Therefore, the use of adrenalectomized mice was inadequate to determine whether CS elevation leads to CTL suppression after HxCB treatment. Daily administration of the glucocorticoid receptor antagonist 17-beta-hydroxy-11-beta-(4-dimethylaminophenyl)-17-alpha-(propanyl )-estra- 4,9-dien-3-one (RU 38486) (150 mg/kg b.w., p.o.) also failed to alter the suppression of CTL activity in HxCB-treated mice; however, spleen cellularity was significantly increased, suggesting functional GCR antagonism. Male mice were more sensitive to HxCB-induced CTL suppression than female mice, and HxCB-induced plasma CS elevation was greater in male mice. Castration failed to reduce the elevation of plasma CS in HxCB-treated male mice. However, castration partially alleviated CTL suppression in HxCB-treated male mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1995

Effect of IL-12 on immune suppression and suppressor cell induction by ultraviolet radiation.

The carcinogenic potential of UV radiation (the primary cause of nonmelanoma skin cancer) is associated with its ability to suppress cell-mediated immune responses. Previous studies have shown that this UV-induced immune suppression is caused by the secretion of immunosuppressive cytokines such as IL-10. Because the effects of IL-10 on the immune response are countered by IL-12, we injected irradiated mice with IL-12 to determine whether it could overcome UV-induced immune suppression. Administration of IL-12 blocked the suppression of delayed-in-time hypersensitivity reactions observed in UV-irradiated animals. Moreover, IL-12 prevented the induction of suppressor T cells, in that adoptive transfer of spleen cells from UV-irradiated mice treated with IL-12 had no effect on the immune response of the recipient mice, whereas transfer of spleen cells from UV-irradiated mice treated with the vehicle inhibited the immune response. In addition, IL-12 neutralized the activity of UV-induced suppressor T cells. Although the adoptive transfer of UV-induced suppressor T cells from irradiated mice suppressed the immune response of the recipient mice, treatment of the recipient mice with IL-12 following the adoptive transfer overcame the immune suppression. The results of these experiments demonstrate that IL-12 can overcome UV-induced immune suppression by preventing the induction of, as well as neutralizing the activity of pre-formed suppressor T cells.

Animals↗
PubMed1991

Dietary histidine increases mouse skin urocanic acid levels and enhances UVB-induced immune suppression of contact hypersensitivity.

Urocanic Acid (UCA) exists in mammalian skin primarily as the trans isomer and is photoisomerized to cis UCA upon UVB absorption. Our previous studies indicated that the photoisomerization of UCA is the initiating event in UBV-induced suppression of cell-mediated immunity (tUCA----cUCA----immune suppression). The purpose of this study was to verify the role of UCA in UV-induced immune suppression of contact hypersensitivity (CHS) in BALB/c mice. Since UCA is a metabolite of the amino acid L-histidine, we reasoned that increased dietary levels of histidine should raise skin tUCA levels. If skin tUCA is the UVB photoreceptor for immune suppression, this increase should enhance UV-induced suppression of CHS. HPLC analysis of skin from BALB/c mice given a histidine-rich diet (10%) showed that the total amount of UCA is significantly higher in these animals than in mice fed a normal diet. Further, levels of suppression of CHS of 3% and 49% in control fed mice, induced by 4.8 and 7.2 kJ/m2 UVB were significantly increased to 21% and 71% respectively in histidine-fed animals at these same UVB doses. These findings provide additional support for the UCA model for immune suppression, and provide the first evidence that UV-induced immune suppression can be enhanced by a dietary component, L-histidine.

Animals↗
PubMed2003

[Mechanism of immune suppression after surgical stress and host defense against infection].

Suppression of cellular immunity secondary to decreased immunocyte function is one of the surgical stress-induced biological responses. Monocytes/macrophages, natural killer (NK) cells, lymphocytes, and neutrophils play an important role in this immune system. These immunity charge cells are expressed through various surface antigens, such as major histocompatibility complex (MHC) class antigens, T cell receptors, and the cytokines interferon-gamma, interleukin (IL)-2, and IL-12. MHC class II antigen expression of monocytes and the cytokine production of CD4+ T cells are decreased after surgical stress. In this immune-suppressed condition, patients after surgical stress can easily experience infectious complications, and therefore the up-regulation of the immune system is necessary to avoid those complications. Recently, the role of natural immunity as a defense system against infection has received attention. The discovery of Toll-like receptor families revealed how the macrophage system cells recognize microorganisms. Furthermore, liver natural killer(NK) cells and NK T cells are important to induce the Th1 immune response in bacterial peritonitis. In this manuscript, we explain the mechanism of immune suppression after surgical stress and the host defense against infection by analyzing cytokine production and surface membrane molecules in mononuclear cells.

Animals↗
PubMed2004

Ablation of hemophilic FVIII inhibitors with FVIII priming, cyclophosphamide immune suppression, and rapid tapering of FVIII immune tolerance.

The efficacy and toxicity of factor VIII (FVIII) priming, cyclophosphamide immune suppression, and rapid tapering of concurrent FVIII immune tolerance for subjects with hemophilic inhibitors were evaluated. Four subjects with hemophilic inhibitors were studied. Before treatment, inhibitors were present for a median of 8 months (mean 13 +/- 14.0 months). The median FVIII inhibitor titer was 16 BU/mL (mean 27.2 +/- 29.2 BU/mL). Following FVIII priming (80.0 +/- 70.2 U/kg), subjects received cyclophosphamide 1,418 +/- 636 mg/M2 i.v. q3 weeks for 4.4 +/- 1.7 courses. Subjects concurrently received a low (6 U/kg/day), moderate (30 U/kg/day), or high (100 U/kg/day) dose of FVIII followed by a rapid taper as the inhibitor titer decreased or resolved. During treatment, the inhibitor titer initially increased but then rapidly declined. Inhibitors resolved in 3.9 +/- 2.9 months. One inhibitor recurred at 2.8 years, but it was successfully re-treated. Effectiveness did not depend on the FVIII dose. Toxicity was minimal. Cyclophosphamide (1,400 mg/M2) administered after a priming dose of FVIII (80 U/kg) i.v. q3 weeks for 2-6 cycles with a rapid taper of concurrently administered daily FVIII as the inhibitor titer falls is an effective approach to hemophilic inhibitor ablation.

Adult↗
PubMed2002

Platelet-activating factor, a molecular sensor for cellular damage, activates systemic immune suppression.

Ultraviolet (UV) radiation plays a critical role in the induction of nonmelanoma skin cancer. UV radiation is also immune suppressive, and the immune suppression induced by UV irradiation has been identified as a major risk factor for skin cancer induction. Previously, we showed that UV exposure activates a cytokine cascade involving prostaglandin (PG)E(2), interleukin (IL)-4, and IL-10 that induces immune suppression. However, the earliest molecular events that occur immediately after UV exposure, especially those upstream of PGE2, are not well defined. UV-irradiated keratinocytes secrete the inflammatory phospholipid mediator, platelet-activating factor (PAF). Because PAF upregulates the production of immunomodulatory compounds, including PGE2, we tested the hypothesis that UV-induced PAF activates cytokine production and initiates UV-induced immune suppression. Both UV and PAF activated cyclooxygenase (COX)-2 and IL-10 reporter gene construct transcription. PAF mimicked the effects of UV in vivo and suppressed delayed-type hypersensitivity (DTH). Furthermore, immune suppression was blocked when UV-irradiated mice were injected with PAF receptor antagonists. In addition to the well-known role of PAF as a proinflammatory lipid mediator, we propose that the PAF receptor senses cellular damage through the recognition of PAF and/or PAF-like molecules, such as oxidized phosphatidylcholine, which activates cytokine transcription and induces systemic immune suppression.

Animals↗