Lack Of Immune Response Research Articles

1089 Lack of immune response following CARDIOsphere(r) infusion in healthy subjects

Eur J Echocardiography Abstracts Supplement, December 2006 Philips Sonos® 5500 and contrast agent (Sonovue®) were used. Images were analyzed by independent sonographers. Sensitivity and specificity for each technique were obtained. Results: Shown in the table. Conclusion: Contrast enhancement echocardiography improves sensitivity of conventional echocardiography to detect segments with left ventricular non compaction cardiomyopathy.

Key gravity‐sensitive signaling pathways drive T‐cell activation

Returning astronauts have experienced altered immune function and increased vulnerability to infection during spaceflights dating back to Apollo and Skylab. Lack of immune response in microgravity occurs at the cellular level. We analyzed differential gene expression to find gravity-dependent genes and pathways. We found inhibited induction of 91 genes in the simulated freefall environment of the random positioning machine. Altered induction of 10 genes regulated by key signaling pathways was verified using real-time RT-PCR. We discovered that impaired induction of early genes regulated primarily by transcription factors NF-kappaB, CREB, ELK, AP-1, and STAT after crosslinking the T-cell receptor contributes to T-cell dysfunction in altered gravity environments. We have previously shown that PKA and PKC are key early regulators in T-cell activation. Since the majority of the genes were regulated by NF-kappaB, CREB, and AP-1, we studied the pathways that regulated these transcription factors. We found that the PKA pathway was down-regulated in vg. In contrast, PI3-K, PKC, and its upstream regulator pLAT were not significantly down-regulated by vectorless gravity. Since NF-kappaB, AP-1, and CREB are all regulated by PKA and are transcription factors predicted by microarray analysis to be involved in the altered gene expression in vectorless gravity, the data suggest that PKA is a key player in the loss of T-cell activation in altered gravity.

IL-12 administration leads to a transient depletion of T cells, B cells, and APCs and concomitant abrogation of the HLA-A2.1-restricted CTL response in transgenic mice.

The injection of a mixture of bona fide T cell epitopes can lead to the occurrence of immunodominance, meaning that the immune response is focused on the recognition of a single epitope or a small portion of the epitopes injected. We have previously demonstrated that the administration of rIL-12 can counteract immunodominance in BALB/c mice. In this study, we show that the administration of rIL-12 to HLA-A2.1 transgenic mice (A2k(b) mice) abrogates specifically the immune response against HLA-A2.1-restricted HIV epitopes in the spleen. This lack of immune response is most probably due to a transient depletion of B cells, T cells, macrophages, and dendritic cells in this organ. Therefore, our study explains the mechanism of immunosuppression by rIL-12 in vivo.

80. Lack of Immune Response Against rtTA Correlates with Long-Term Doxycycline-Regulated Transgene Expression in Nonhuman Primate after Intramuscular Injection of Recombinant Adeno-Associated Virus

80. Lack of Immune Response Against rtTA Correlates with Long-Term Doxycycline-Regulated Transgene Expression in Nonhuman Primate after Intramuscular Injection of Recombinant Adeno-Associated Virus

Lack of immune responses to immediate or delayed implanted allogeneic and xenogeneic Schwann cell suspensions

Lack of immune responses to immediate or delayed implanted allogeneic and xenogeneic Schwann cell suspensions

Vaccination with peptides from MHC class II beta chain hypervariable region causes allele-specific suppression of EAE

<h2>Abstract</h2> In our earlier studies we showed that successful immunotherapy of EAE in SJL/J mice can be achieved either by the use of antibodies to MHC class II antigens or by vaccination with synthetic peptide analogs of the beta chain of MHC class II molecules. We proposed that inhibition of EAE following vaccination with synthetic peptides derived from the beta chain of mouse I-A, was in part due to the generation of auto-anti-MHC class II antibodies that interfered with T cell sensitization. In our present study we show that suppression of EAE following vaccination results in poor sensitization of MBP reactive T cells, and that the lack of immune response is allele-specific. In Fl(SJL^{I−A^s} × Balb/c^{I−A^d}) mice, in which susceptibility to EAE is linked closely to the I-A^s allele, vaccination with peptides from beta chain of I-A^s results in inhibition of proliferative response to MBP and prevents the development of EAE. Vaccination with peptide from the beta chain of I-A^d did not affect either the development of immune response to MBP or the induction of EAE, indicating allele-specific suppression. Since global immunosuppression is not induced by vaccination with I-A peptides, we propose that this strategy can be extended to human autoimmune diseases wherein a clear association between certain MHC class II alleles and autoimmune disease is evident.

Vaccination with peptides from MHC class II beta chain hypervariable region causes allele-specific suppression of EAE

In our earlier studies we showed that successful immunotherapy of EAE in SJL/J mice can be achieved either by the use of antibodies to MHC class II antigens or by vaccination with synthetic peptide analogs of the beta chain of MHC class II molecules. We proposed that inhibition of EAE following vaccination with synthetic peptides derived from the beta chain of mouse I-A, was in part due to the generation of auto-anti-MHC class II antibodies that interfered with T cell sensitization. In our present study we show that suppression of EAE following vaccination results in poor sensitization of MBP reactive T cells, and that the lack of immune response is allele-specific. In Fl(SJL I−A s × Balb/c I−A d ) mice, in which susceptibility to EAE is linked closely to the I-A s allele, vaccination with peptides from beta chain of I-A s results in inhibition of proliferative response to MBP and prevents the development of EAE. Vaccination with peptide from the beta chain of I-A d did not affect either the development of immune response to MBP or the induction of EAE, indicating allele-specific suppression. Since global immunosuppression is not induced by vaccination with I-A peptides, we propose that this strategy can be extended to human autoimmune diseases wherein a clear association between certain MHC class II alleles and autoimmune disease is evident.

Effect of age and sex on the induction and elicitation of allergic contact dermatitis

This article reviews the effect of age and sex on the induction and elicitation of allergic contact dermatitis (ACD). We found that the incidence of ACD in childhood is lower than in adults; this may be explained by less exposure to allergens, lack of immune response and limited patch test studies in this age group. In the elderly, there is an age-dependent decrease in the incidence of ACD, with decreased sensitization to new allergens and waning responses in previously sensitized subjects. There is extensive controversy about the effect of sex differences in ACD. The induction phases of ACD in both sexes are different due to differences in exposure to the allergens from occupations, habits and cultures. Differences in elicitation phases of ACD in both sexes are not confirmed. Women tend to have a higher incidence of ACD and higher immunologic response to exposure allergens than men. Thus we can only imprecisely define the effect of age and sex on the induction and elicitation of ACD. Further prospective studies should be done to answer these questions.

Anti-donor antibody class switching after liver transplantation.

The humoral immune response directed against donor antigens was monitored by flow cytometry in 17 liver transplant patients using donor leukocytes as targets. Overall, donor-specific antibodies developed in 15 patients; these included all 9 patients who had experienced a biopsy-proven episode of acute rejection and 6 out of 8 patients who had not had an acute episode of rejection. The isotypes of the donor-specific antibodies in the 9 patients who had experienced an early episode of acute rejection were IgG in 8 patients, IgE in 8 patients, and IgA in 6 patients; all 9 patients had IgE and/or IgA antibodies. In the 6 patients who showed no evidence of acute clinical rejection but nevertheless developed donor-specific antibodies, the isotype was IgM associated in 5 of them, with an immunoglobulin class switching to the IgG isotype; none of these patients had antibodies of the IgA or IgE isotype. These results indicate that the lack of rejection of a liver allograft does not necessarily result from a lack of immune response against donor antigens. Rather, the distinct pattern of (cytokine dependent) immunoglobulin class switching suggests that the lack of liver graft rejection may be the result of an immune activation pathway distinct from that resulting in graft rejection.

Lack of Immune Response to Mouse IgG in Hemophilia A Patients Treated Chronically with Monoclate®, a Monoclonal Antibody Affinity Purified Factor VIII Preparation

Hemophilia A is caused by factor VIII deficiency that historically has been treated with either a cryoprecipitate fraction of serum or factor VIII concentrate. Recently, the availability of affinity isolated factor VIII (Monoclate) has allowed for a highly purified preparation for the chronic therapy of hemophilia A. This factor VIII preparation contains a trace quantity (less than 50 ng/100 I. U.) of mouse IgG. Immunoassays for the measurement of human IgG, IgM and IgE anti-mouse IgG antibody (HAMA) were developed and used to measure HAMA levels in hemophilia A patients undergoing chronic therapy with Monoclate in three different clinical studies. Natural antibodies to mouse IgG were observed in patient sera prior to Monoclate infusion. Data is presented demonstrating that induction of HAMA upon Monoclate treatment does not occur. The low level of mouse IgG contained in Monoclate appears to be below the threshold of immunogenicity. Most importantly, clinical symptoms related to hypersensitivity or anaphylaxis were never observed in any patient undergoing chronic therapy with Monoclate in these clinical studies.

End-stage dilated cardiomyopathy. Persistence of enterovirus RNA in myocardium at cardiac transplantation and lack of immune response.

Tissue from the explanted hearts of 21 patients with idiopathic dilated cardiomyopathy or 19 patients with other specific heart muscle diseases were investigated for presence of enterovirus-specific RNA with an enterovirus group-specific cDNA probe. This was complementary to coxsackievirus B2 RNA sequences between nucleotide numbers 6,550 and 7,400, which are highly conserved between enteroviruses. Hearts from six patients with dilated cardiomyopathy and one patient with ischemic heart disease were found to contain virus RNA. Serology revealed that only one patient (dilated cardiomyopathy group) was positive for coxsackievirus B-specific IgM but negative for virus RNA in the myocardium. Quantitation of leukocytes and T-lymphocytes in the myocardium and expression of major histocompatibility locus antigens revealed no significant differences associated with persistence of virus RNA. These data demonstrate that enterovirus RNA persists in myocardium of a significant proportion of patients with end-stage dilated cardiomyopathy in the absence of a continuing cell-mediated or humoral immune response.

In vivo and in vitro immunosuppressions in mice by a 100-110-Kd fraction from boar seminal plasma.

The activity of a 100-110-Kd immunosuppressive fraction (ISF), isolated from boar seminal plasma, was investigated in mice. In vitro, this fraction was found to inhibit a unidirectional mixed lymphocyte response and cell-mediated lymphocytotoxicity, as well as antisheep red blood cells (T-dependent) and antitrinitrophenylated lipopolysaccharide (T-independent) responses. The ISF also inhibited the macrophage phagocytosis of erythrocytes coated with IgG antibodies, but it did not suppress the natural killer activity. In vivo, ISF was found to lower both the primary responses to T-dependent and to T-independent antigens. Trypsin or pronase digestion of ISF provided active molecules of 30 Kd or 2-5 Kd respectively, thus showing that the activity is due to a protein. This ISF factor, capable of suppressing a wide variety of immune functions and remaining active after cleavage by proteases, could play a role in the lack of immune response against the spermatozoa present in the sow genital tract after intercourse. The use of this factor as a therapeutic agent in humans could eventually be considered after further molecular characterization.

Lack of Immune Response to Retinal Antigens in Dystrophic Rats

The immunological activity to ocular antigens has been investigated in dystrophic and normal rats at various stages of age by indirect immunofluorescence and radiometric ear tests. In dystrophic rats, antibodies to rhodopsin, uveal pigment granules or soluble retinal proteins could not be detected, nor was a difference found in cell-mediated immune activity to these antigens between dystrophic and normal rats. The differences between the findings in human retinitis pigmentosa and in rat retinal degeneration are discussed.

Metastasis in the nude rat associated with lack of immune response.

Metastasis in the nude rat associated with lack of immune response.

Delayed Cutaneous Hypersensitivity in Patients with Prostatic Adenocarcinoma

Cell-mediated immunocompetence of patients seen for followup of adenocarcinoma of the prostate is evaluated using dinitrochlorobenzene as a contact sensitizing agent. The immune status is correlated with the presence or absence of metastatic disease. A highly significant correlation is found between the lack of immune response and the presence of metastatic carcinoma, suggesting that immunotherapy will be useful in the treatment of carcinoma of the prostate.

Research Note: Immunologic Response of Chicks to Inactivated Newcastle Disease Virus

One of the major problems in controlling Newcastle Disease (NDV) is the lack of immune response of young chicks up to 21 days old. Although this age group is very sensitive to infection, maternal antibodies and presumed immunologic immaturity make it difficult to induce an adequate immune response (4,5). An additional problem is variability in the level of maternal antibodies (1,2): when some chicks are still protected by maternal antibodies others are at a high risk of infection because of either a low level or complete loss of maternal antibodies (Zakey-Rones and Levy, unpublished). To investigate this problem without virus multiplication, an inactive vaccine was used. The vaccine used contained an equivalent of 108-3 EID5o of virus prepared by inactivating the NDV, strain Israel (kindly given to us by Dr. A. Kohn, Israel Institute for Biological Research, Nes-Ziona, Israel) with /-propiolactone and mixed with incomplete Freund's adjuvant (6). We had previously found that this dose of antigen stimulates an adequate antibody response in chickens and confers resistance against challenge with a highly virulent strain (Zakay-Rones and Levy, in preparation). Groups of chicks 3-5 days old, the offspring of unimmunized chickens and lacking maternal antibodies, were immunized intramuscularly with inactive oil-adjuvant vaccine. Antibody response was determined by the hemagglutination-inhibition (HI) test (Table 1). Chicks in group 1, completely lacking maternal antibodies, responded to a 108 3 EID5o dose of antigen with high titers of HI antibodies. The antibody titers remained at a high level for as long as 3 months. In group III, in the presence of maternal antibodies, a very low titer of HI antibodies could be detected after