SEARCH · Search PubMed

Results for “Immunity, Natural”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

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

At least 523 records · Page 29Linked to original sources

PubMed1998

Development of Th1 and Th2 populations and the nature of immune responses to hepatitis B virus DNA vaccines can be modulated by codelivery of various cytokine genes.

In this study, we provide direct evidence that the magnitude and nature of the immune response to a DNA vaccine can be differentially regulated by codelivery of various mouse cytokine genes. Mice immunized with a hepatitis B virus (HBV) DNA vaccine and the IL-12 or IFN-gamma gene exhibited a significant enhancement of Th1 cells and increased production of anti-HBV surface IgG2a Ab, as well as a marked inhibition of Th2 cells and decreased production of IgG1 Ab. In contrast, coinjection of the IL-4 gene significantly enhanced the development of specific Th2 cells and increased production of IgG1 Ab, whereas Th1 differentiation and IgG2a production were suppressed. Coinjection of the IL-2 or the granulocyte-macrophage-CSF gene enhanced the development of Th1 cells, while the development of Th2 cells was not affected, and the production of IgG1 and IgG2a Ab were both increased. The CTL activity induced by HBV DNA vaccination was most significantly enhanced by codelivery of the IL-12 or IFN-gamma gene, followed by the IL-2 or granulocyte-macrophage-CSF gene, whereas codelivery of the IL-4 gene suppressed the activity. When challenged with HBV surface Ag (HBsAg)-expressing syngeneic tumors, significant reduction of tumor growth was observed in mice that were coadministered the IL-12 gene but not the IL-4 gene. Taken together, these results demonstrate that application of a cytokine gene in a DNA vaccine formulation can influence the differentiation of Th cells as well as the nature of an immune response and may thus provide a strategy to improve its prophylactic and therapeutic efficacy.

Adjuvants, Immunologic↗

PubMed2001

Cellular HIV-1 immune responses in natural infection and after genetic immunization.

By eliminating infected cells, virus-specific cytotoxic T-lymphocytes (CTL) play a central role in host protection. Many studies to date seem to support the concept that human immunodeficiency virus (HIV)-specific CTL responses contribute to the control of viral replication, and thus delay the onset of disease. The feasibility of improving the virus-specific T-cell immunity by immunizing during the asymptomatic phase of infection has been studied in man. DNA vaccination is a novel strategy, involving direct inoculation of genetic material that is capable of producing antigen intracellularly for presentation to CTL. Such DNA-based immunization has been shown in animal models to be effective for the induction of both cellular and humoral immune responses as well as for protection from infectious challenge. This article reviews the cell-mediated immune responses in natural HIV-1 infection and the induction by DNA vaccination in humans.

AIDS Vaccines↗

PubMed2001

Loss of maternally derived human herpesvirus-6 immunity and natural infection in Argentinian infants.

BACKGROUND: Human herpesvirus-6 (HHV-6) infection is widespread throughout the world. No data are available in Argentina about the loss of maternally derived HHV-6 immunity and natural infection in infants. METHODS: A population of 100 pregnant women and 407 children between 1 and 15 months of age were assayed by indirect immunofluorescence to detect and quantify specific IgG anti-human herpesvirus-6 (anti-HHV-6) antibodies in Córdoba City, Argentina. RESULTS: There was no significant difference in the positive rate between infants aged 1 to 9 months (range, 43.6 35.5%) and pregnant women (37%). Seropositive ratio dropped in the 10-month group (23.33% seropositive) and rose sharply in the 11-month group (38.89%), 12-month (60.61%), and 13- to 15-month group (63.46%). The geometric mean titer (GMT) for infants in the 12 to 15 months age group (23.4 41.64) was significantly higher than the GMT for infants 10 months of age (11.04) (P < 0.05 with the Tukey-HSD test). CONCLUSIONS: This study shows a significant association between loss of passive HHV-6 antibody and age among infants. The results support evidence that HHV-6 enters the susceptible population at 11 months, leading to a high prevalence of antibodies in children between 13 and 15 months of age.

Adolescent↗

PubMed1982

Subacute sclerosing panencephalitis after passive immunization and natural measles infection: role of antibody in persistence of measles virus.

Subacute sclerosing panencephalitis (SSPE) developed in a patient in whom natural measles infection was anteceded by immunization with measles immune serum globulin (ISG). This observation prompted experimental studies of the role of antibody in viral persistence. When Balb/c mice were infected with the hamster neurotropic measles virus, acute encephalopathy was fatal in 80% of the animals. When measles antibody was administered 3 days after virus inoculation, the acute disease was abolished and subacute encephalitis had a 30% mortality. The subacute disease was characterized by the presence of neuronal viral antigen, meningitis, and encephalitis. Induction of viral persistence was therefore a consequence of antibody transfer during viral infection. Caution is advised in human prophylaxis with immune globulin.

Animals↗

PubMed1992

Comparison between natural and immunized anti-GM1 antibodies analyzed by marker releasing rate assay with liposome.

Naturally occurring rabbit anti-GM1 was compared with immunized induced anti-GM1 antibody in the same individual rabbits by the characterization of immune potency determined by complement-dependent damage to liposomes containing GM1 as antigen. Antigen-antibody reaction was the rate determining step in this assay. The maximum rate was measured by the first derivative conversion monitoring in spectrophotometry and the maximum level of marker released was measured by the conventional method described previously. When the concentration of sera required to get fifty percent of maximum values in each assay were compared, the ratios (rate assay/conventional assay) were 5.7 to 10.0 in natural antibodies and 3.2 to 2.3 in immunized induced antibodies, respectively. Furthermore, the maximum rate of marker release from liposome was not correlated with the maximum level of marker released depended on the sources of antibodies. These results suggest that natural antibody, even the titer was high in conventional liposome assay, has different characteristics compared with the immunized induced antibody.

Animals↗

PubMed2005

Defect of a subpopulation of natural killer immune cells in Graves' disease and Hashimoto's thyroiditis: normalizing effect of dehydroepiandrosterone sulfate.

BACKGROUND: The study of the natural killer (NK) immune compartment could provide important findings to help in the understanding of some of the pathogenetic mechanisms related to autoimmune thyroid diseases (Graves' disease (GD) and Hashimoto's thyroiditis (HT)). Within this context, it was suggested that alterations in NK cell cytotoxicity (NKCC) and NK production of cytokines might occur in subjects with GD and HT, whereas the normalization of NK functions could potentially contribute to the prevention of the onset or the progression of both diseases. OBJECTIVE: Due to the hypothesis of alterations in NK in autoimmune thyroid diseases, we were interested to evaluate NKCC in GD and HT patients and to modulate NK function and secretory activity with cytokines and dehydroepiandrosterone sulfate (DHEAS) in an attempt to normalize NK cell defect. DESIGN: We studied 13 patients with recent onset Graves' disease, 11 patients with Hashimoto's thyroiditis at first diagnosis and 15 age-matched healthy subjects. METHODS: NK cells were concentrated at a density of 7.75x10(6) cells/ml by negative immunomagnetic cell separation and validated by FACScan as CD16+/CD56+cells. NK cells were incubated with interleukin-2 (IL-2) and interferon-beta (IFN-beta) and co-incubated with DHEAS at different molar concentrations for measuring NKCC and the secretory pattern of tumor necrosis factor-alpha (TNF-alpha) from NK cells. RESULTS: Lower spontaneous, IL-2- and IFN-beta-modulated NKCC was demonstrated in GD and HT patients compared with healthy subjects (P<0.001). A decrease in spontaneous and IL-2-modulated TNF-alpha release from NK cells was also found in both groups of patients (P<0.001). The co-incubation of NK cells with IL-2/IFN-beta+DHEAS at different molar concentrations (from 10(-8) to 10(-5) M/ml/NK cells) promptly normalized NKCC and TNF-alpha secretion in GD and HT patients. CONCLUSIONS: A functional defect of a subpopulation of NK immune cells, involving both NKCC and the secretory activity, was demonstrated in newly-diagnosed GD and HT patients. This defect can be reversed by a dose-dependent treatment with DHEAS. The impairment of NK cell activity in autoimmune thyroid diseases could potentially determine a critical expansion of T/B-cell immune compartments leading to the generation of autoantibodies and to the pathogenesis of thyroid autoimmunity.

Adjuvants, Immunologic↗

PubMed1972

Natural and immune antibodies for Vibrio fetus in serum and secretions of cattle.

Naturally occurring antibodies for Vibrio fetus with whole-cell and O antigen specificities were detected in sera of mature cattle by means of the agglutination and indirect immunofluorescence reactions. O antibodies occurred in each of 21 sera examined, and whole-cell antibodies, in lower concentrations, occurred in 15 of the 21 sera. Natural antibodies were detected in the immunoglobulin G, M, and A (IgG, IgM, IgA) classes. Parenteral immunization with whole cells in Freund's complete adjuvant caused an increase in antibodies, predominantly IgG, with both whole-cell and O specificities; genital infection produced minimal alterations in levels of serum antibody. O antibodies, predominantly of the IgA class, occurred in nasal secretions of most of these animals but only infrequently in saliva or tears. Nasal secretion titers of O antibodies fluctuated widely from week to week but appeared to be unaffected by parenteral immunization or experimental infection. It is hypothesized that the nasal passages serve as a site of antigenic stimulation and synthesis of naturally occurring V. fetus antibodies.

Animals↗

PubMed1998

Evaluation of the Galalpha1-3Gal epitope as a host modification factor eliciting natural humoral immunity to enveloped viruses.

Human sera contain high levels of natural antibody (Ab) to Galalpha1-3Gal, a terminal glycosidic structure expressed on the surface of cells of mammals other than Old World primates. Incorporation of this determinant onto retroviral membranes by passage of viruses in cells encoding alpha-1-3-galactosyltransferase (GT) renders retroviruses sensitive to lysis by natural Ab and complement in normal human serum (NHS). Plasma membrane-budding viruses representing four additional virus groups were examined for their sensitivities to serum inactivation after passage through human cell lines that lack a functional GT or human cells expressing recombinant porcine GT. The inactivation of lymphocytic choriomeningitis virus (LCMV) by NHS directly correlated with host modification of the virus via expression of Galalpha1-3Gal and was blocked by incorporation of soluble Galalpha1-3Gal disaccharide into the inactivation assay. GT-deficient mice immunized to make high levels of Ab to Galalpha1-3Gal (anti-Gal Ab) were tested for resistance to LCMV passaged in GT-expressing cells. Resistance was not observed, but in vitro analyses of the mouse immune sera revealed that the antiviral activity of the sera was insufficient to eliminate LCMV infectivity on its natural targets of infection, macrophages, which express receptors for Ab and complement. Newcastle disease virus and vesicular stomatitis virus (VSV) were inactivated by NHS regardless of cell passage history, whereas Sindbis virus (SV) passaged in human cells resisted inactivation. Both VSV and SV passaged in Galalpha1-3Gal-expressing human cells incorporated this sugar moiety onto their major envelope glycoproteins. SV passaged in mouse cells expressing Galalpha1-3Gal was moderately sensitive to inactivation by NHS. These results indicate that enveloped viruses expressing Galalpha1-3Gal differ in their sensitivities to NHS and that a potent complement source, such as that in NHS, is required for efficient inactivation of sensitive viruses in vitro and in vivo.

Animals↗

PubMed1994

Enhancement of natural killer activity and interferon induction by different acyclic nucleoside phosphonates.

Acyclic nucleoside phosphonate (ANP) analogues are a class of compounds with potent activity against herpesviruses and/or retroviruses. Our preliminary experiments have shown that 9-(2-phosphonylmethoxyethyl)adenine (PMEA), a prototype of the ANP family, enhances some parameters of natural immunity. In this paper we have evaluated the effect of different schedules of administration of PMEA and other ANP analogues of clinical interest upon natural killer (NK) activity and interferon (IFN) production in a mouse model. The results show that PMEA significantly enhances NK activity and interferon production. Other ANP analogues tested in our system, i.e., 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP), and 9-(3-fluoro-2-phosphonylmethoxypropyl)adenine (FPMPA), similarly induced enhancement of natural immunity. The immunomodulating effect of PMEA was even more pronounced with a single administration compared to repeated administrations of the drug. Dose-dependent enhancement of NK activity and IFN production could also be demonstrated during chronic administration of PMEA (more resembling to what will be the schedule of administration of this drug in patients). Overall, the data here presented suggest that the enhancement of some natural immune functions induced by ANP analogues may add to the direct antiviral activity of these drugs against retroviruses and herpesviruses, and thus may be able to increase the host resistance against viral infections.

Adenine↗

PubMed1991

A species/strain comparison of hepatic natural lymphocytotoxic activities in rats and mice.

The natural killer (NK) and natural cytotoxic (NC) cell activities in livers from certain rat and mouse strains were compared. This included the two rodent strains used in animal carcinogenicity bioassays, i.e. Fischer 344 and B6C3F1 mice. Sprague-Dawley and Fischer 344 rats exhibited high hepatic NK activity, which was greater than the levels seen in all of the five mouse strains studied. However, the hepatic NC activity in rats was comparable to the activities observed in C57BL and BALB/c mice. An inverse relationship was observed between the two tumoricidal activities in all but one of the mouse strains examined; that is (at 8 weeks of age), NK activity: C3H greater than B6C3F1 greater than CBA greater than BALB/c; NC activity: BALB/c much greater than CBA greater than B6C3F1 greater than C3H. The C57BL mouse strain was the only strain to express both activities at comparatively high levels. Female mice exhibited a similar profile of cytotoxic activities. Rats also possessed high activities of a presently ill-defined tumoricidal activity, this being the spontaneous P815 mastocytoma killing by unstimulated effector cells, over an 18 h period. Both adherent and nonadherent effector cells from rat livers, but only the nonadherent cell population isolated from male mouse livers, exhibited this activity which may represent a distinct hepato-specific population of natural lymphocytotoxic effector cells. The tumoricidal activities in liver-derived cells were greater than those of effector cells isolated from the spleen. The differences in natural immunity reported in this study may be related to the varying background incidences of hepatic tumors, i.e. the mouse strains susceptible to high background incidences of liver tumors have relatively low natural immunity, whereas the two mouse strains resistant to hepatic tumors possess high levels of at least one hepatic NLC activity. Similarly, rats have relatively low hepatic tumor rates and high levels of hepatic natural immunity.

Age Factors↗

PubMed1999

Role of acquired immunity and natural age resistance on course of Isospora suis coccidiosis in nursing piglets.

Thirty-two piglets from three litters were experimentally inoculated with 200000 sporulated oocysts of Isospora suis at 3 days of age and/or rechallenged at 19 days of age or primary inoculated at 19 days of age, to compare the role of acquired immunity and natural age resistance on the course of coccidiosis. Twelve piglets were not inoculated and served as a control. Following challenge, the signs of coccidiosis characterised by clinical symptoms, oocysts shedding and weekly weights were similar to those which occurred in piglets primary inoculated at 19 days of age. This comparison suggests that maturation of non-specific components of the immune system plays a more important role in the resistance of neonatal piglets to I. suis infection than specific immune mechanisms.

Aging↗

PubMed2006

In a bovine model of onchocerciasis, protective immunity exists naturally, is absent in drug-cured hosts, and is induced by vaccination.

Onchocerciasis (river blindness) is a major parasitic disease of humans in sub-Saharan Africa caused by the microfilarial stage of the nematode Onchocerca volvulus. Using Onchocerca ochengi, a closely related species which infects cattle and is transmitted by the same black fly vector (Simulium damnosum sensu lato) as O. volvulus, we have conducted longitudinal studies after either natural field exposure or experimental infection to determine whether, and under what circumstances, protective immunity exists in onchocerciasis. On the basis of the adult worm burdens (nodules) observed, we determined that cattle reared in endemic areas without detectable parasites (putatively immune) were significantly less susceptible to heavy field challenge than age-matched, naïve controls (P = 0.002), whereas patently infected cattle, cured of infection by adulticide treatment with melarsomine, were fully susceptible. Cattle immunized with irradiated third-stage larvae were significantly protected against experimental challenge (100% reduction in median nodule load, P = 0.003), and vaccination also conferred resistance to severe and prolonged field challenge (64% reduction in median nodule load, P = 0.053; and a significant reduction in microfilarial positivity rates and density, P < 0.05). These results constitute evidence of protective immunity in a naturally evolved host-Onchocerca sp. relationship and provide proof-of-principle for immunoprophylaxis under experimental and field conditions.

Animals↗

PubMed1999

Genetic background determines the nature of immune responses and experimental immune-mediated blepharoconjunctivitis (EC).

PURPOSE: Experimental immune-mediated blepharoconjunctivitis (EC) was induced in Lewis rats by immunization with ovalbumin (OVA) in complete Freund's adjuvant (CFA) or aluminum hydroxide [Al(OH)3]. To investigate the affect of genetic factors on the susceptibility of EC, we tested different strains of rats for the development of EC. METHODS: Lewis and Brown Norway (BN) rats were immunized once with 100 microg of OVA in CFA or Al(OH)3. Three weeks later they were challenged with OVA in eye drops; 24 hours after the challenge they were sacrificed and their eyes, blood, and lymph nodes were harvested for histological studies, measurement of OVA-specific antibodies (IgG, IgG1, IgG2a, IgE), and proliferation or cytokine assay, respectively. ELISA was used to detect OVA-specific IgG; passive cutaneous anaphylaxis was used for detecting IgE. RESULTS: EC, OVA-specific IgG, and cellular immunity were induced in Lewis rats by using either adjuvant, whereas IgE was not produced by either adjuvant. In contrast, IgE was produced in BN rats using either adjuvant, whereas cellular immunity was evoked only when CFA was used. Less cellular infiltration as well as cellular proliferation was detected in BN rats immunized with Al(OH)3. In both strains, Al(OH)3 induced a higher IgG1/IgG2a ratio than did CFA. More interferon-gamma by stimulation with OVA was noted in Lewis rats compared to BN rats, whereas interleukin-4 was detected only in BN rats. CONCLUSIONS: The severity of EC evaluated by cellular infiltration was dependent on OVA-specific cellular immunity. Genetic background is more important than adjuvants in determining the nature of EC and immunity.

Aluminum Hydroxide↗

PubMed1999

[Mistletoe therapy from the pharmacologic perspective].

Because of their cytostatic/apoptotic and immunomodulatory effects mistletoe extracts are often applied in tumour patients. Recent experimental data suggest that the mistletoe lectins Viscum album agglutinin (VAA)-I and -II are play an important role in the efficacy of mistletoe therapy. VAA-I and -II are members of the type-II ribosome-inactivating proteins. VAA-I has been shown to induce cytostatic effects in cultures of various eukaryotic cells in vitro. In 24-hour cultures of human peripheral lymphocytes, flow-cytometric investigations with propidium iodide (PI) in hypotonic buffer and quantitative assessment of DNA breaks with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end-labeling (TUNEL) assay were carried out; they revealed a dose-dependent VAA-I-induced apoptosis (lectin concentrations between 10 ng/ml and 1 microg/ml). In 24-hour cultures of peripheral blood mononuclear cells (PBMC), VAA-I in non-cytotoxic concentrations (1+/-10 ng/ml) induced mRNA expression and enhanced the secretion of proinflammatory cytokines. The stimulation of NK cells by VAA-I in vitro was enhanced in additive manner by the combination of VAA-I with IL-2 and IL-12. In culture of PBMC and bone marrow CD34+ cells coincubation of VAA-I with other haematopoietic growth factors induced a dose-dependent increase in clonogenic growth. In cancer patients the mechanisms of natural immunity, believed to be essential for their survival, are often significantly decreased. VAA-I and standardized mistletoe extracts are able to stimulate the cellular parameters of natural immunity with a bell-shaped curve of efficacy. Studies in animal models suggest that application of 0.5-3 ng/kg VAA-I twice a week is effective in sustaining the elevation of the number and activity of peripheral blood NK cells. These parameters often exhibit high intrinsic fluctuations, in healthy persons, however, blind crossover studies reveal an optimal lectin dose of about 0.5 and 1 ng/kg bw, suggesting a potential use of mistletoe preparations as a modulator of the natural immune system. Selective apoptotic effects of VAA-I may represent a novel approach for pharmacological manipulation of the balance between cell growth and programmed cell death. Appropriate combination of immunomodulatory and cytotoxic doses may open new clinical perspectives in the mistletoe therapy.

Bone Marrow Cells↗

PubMed1985

Prevention of congenital rubella in Iceland by antibody screening and immunization of seronegative females.

A programme to eradicate congenital rubella from Iceland was started in 1979, based on (1) screening of all females aged 12-45 years for rubella antibodies and (2) vaccination of all seronegative persons with the RA/27/3 rubella vaccine, given free of charge. Thus, individual protection was offered to all who needed it. The collection of serum samples was planned to last for 2 years while, simultaneously, the already established rubella screening and immunization programmes for 12-year-old schoolgirls and pregnant women continued.During assessment in 1983, 95.2% of females in the first 7 age groups (by now aged 14-20 years) participating in the school programme had been tested and 80.4% of them were found to be naturally immune. Of the seronegatives, 93.7% were subsequently vaccinated, thus giving an overall immunity rate of 98.8%. Among the women in the peak of the childbearing period (by now aged 21-35 years), 84.4% had been tested and 92.7% were found to be naturally immune; vaccination of 61.4% of seronegative individuals then gave an overall immunity rate of 97.2% for this age group.If it is assumed that the natural immunity rate of females still untested is like that of the above groups, then the percentage of non-immune persons is at present 2.1% in the younger group and 3.4% in the older.

Adolescent↗

PubMed1991

Immunomodulatory activity of 9-(2-phosphonylmethoxyethyl)adenine (PMEA), a potent anti-HIV nucleotide analogue, on in vivo murine models.

In order to evaluate the influence of antiviral nucleoside analogues upon the natural immune system, we investigated the immunomodulatory activity of 9-(2-phosphonylmethoxyethyl)adenine (PMEA), a nucleotide analogue with potent anti-HIV and anti-herpes activity, in a murine system. C57BL/6 mice were inoculated intraperitoneally with 10, 25 and 50 mg PMEA/kg. Mononuclear cells were isolated from their spleens, and some natural immune functions were evaluated. The results show that PMEA significantly increases the levels of natural killer (NK)-cell cytotoxicity. We also found that alpha/beta IFN production was substantially increased in PMEA-treated mice, while both IL-1 and IL-2 production was decreased. Thus, PMEA can increase some natural immunity functions, such as NK activity and IFN production. These results suggest that PMEA might be active in vivo against HIV and herpes viruses both as an immunomodulator and as an antiviral compound.

Adenine↗

PubMed1992

Kinetics and viral protein specificity of the cytotoxic T lymphocyte response in healthy adults immunized with live attenuated varicella vaccine.

The cytotoxic T lymphocyte (CTL) response was evaluated in adults given live attenuated varicella vaccine, using target cells expressing varicella-zoster virus (VZV) immediate-early protein (IE62) or VZV glycoproteins gpI, gpIV, or gpV to determine viral protein specificity. The frequency of CTL that recognized IE62 was 1:171,000 +/- 46,000 SE in subjects tested 10 days to 8 weeks after the initial vaccine dose; the induction of CTL specific for gpI was equivalent. CTL recognition of VZV proteins was mediated by CD4+ or CD8+ cells. CTL recognition of IE62 and gpIV persisted in vaccinees (tested approximately 4 years later) and was comparable to that in the naturally immune. The mean frequency of CTL specific for gpV was lower (but not significantly) in vaccinees than in naturally immune subjects. Assay of responder cell frequencies showed persistence of equivalent numbers of T lymphocytes that recognized IE62 and gpI in vaccinees and naturally immune subjects. Immunization with this vaccine elicited memory T lymphocyte responses to VZV comparable to those induced by natural infection.

Antibodies, Viral↗

PubMed2006

An alternative and effective HIV vaccination approach based on inhibition of antigen presentation attenuators in dendritic cells.

BACKGROUND: Current efforts to develop HIV vaccines that seek to stimulate immune responses have been disappointing, underscoring the inability of natural immune responses to control HIV-1 infection. Here we tested an alternative strategy to induce anti-HIV immune responses by inhibiting a host's natural immune inhibitor. METHODS AND FINDINGS: We used small interfering RNA (siRNA) to inhibit suppressor of cytokine signaling (SOCS) 1, a key negative regulator of the JAK/STAT pathway, and investigated the effect of this silencing on the ability of dendritic cells (DCs) to induce anti-HIV-1 immunity. We found that SOCS1-silenced DCs broadly induced enhanced HIV-1 envelope (Env)-specific CD8+ cytotoxic T lymphocytes and CD4+ T helper cells, as well as antibody responses, in mice. Importantly, SOCS1-silenced DCs were more resistant to HIV Env-mediated suppression and were capable of inducing memory HIV Env-specific antibody and T cell responses. SOCS1-restricted signaling, as well as production of proinflammatory cytokines such as interleukin-12 by DCs, play a critical role in regulating the anti-HIV immune response. Furthermore, the potency of HIV DNA vaccination is significantly enhanced by coimmunization with SOCS1 siRNA expressor DNA. CONCLUSIONS: This study demonstrates that SOCS1 functions as an antigen presentation attenuator to control both HIV-1-specific humoral and cellular responses. This study represents the first, to our knowledge, attempt to elicit HIV-specific T cell and antibody responses by inhibiting a host's antigen presentation attenuator, which may open a new and alternative avenue to develop effective therapeutic and prophylactic HIV vaccines.

AIDS Vaccines↗