A macrophage invasion mechanism for mycobacteria implicating the extracellular domain of CD43.

We studied the role of CD43 (leukosialin/sialophorin), the negatively charged sialoglycoprotein of leukocytes, in the binding of mycobacteria to host cells. CD43-transfected HeLa cells bound Mycobacterium avium, but not Salmonella typhimurium or Shigella flexneri. Quantitative bacteriology showed that macrophages (M(phi)) from wild-type mice (CD43(+/+)) bound M. avium, Mycobacterium bovis (bacillus Calmette-Guérin), and Mycobacterium tuberculosis (strain H37Rv), whereas M(phi) from CD43 knockout mice (CD43(-/)-) did not. Fluorescence microscopy demonstrated that the associated M. avium had been ingested by the CD43(+/+) M(phi). The inability of CD43(-/)- M(phi) to bind M. avium could be restored by addition of galactoglycoprotein (Galgp), the extracellular mucin portion of CD43. The effect of Galgp is not due to opsonization of the bacteria, but required its interaction with the M(phi) other mucins had no effect. CD43 expression by the M(phi) was also required for optimal induction by M. avium of tumor necrosis factor (TNF)-alpha production, which likewise could be reconstituted by Galgp. In contrast, interleukin (IL)-10 production by M. avium-infected M(phi) was CD43 independent, demonstrating discordant regulation of TNF-alpha and IL-10. These findings describe a novel role of CD43 in promoting stable interaction of mycobacteria with receptors on the M(phi) enabling the cells to respond specifically with TNF-alpha production.

Macrophage apoptosis in mycobacterial infections.

Mycobacterial diseases are a major public health concern. In the case of tuberculosis, the problem has been acerbated due to the emergence of drug-resistant strains of Mycobacterium tuberculosis, and Mycobacterium avium is the major opportunistic pathogen in HIV-1 infection in the United States. M. tuberculosis and M. avium replicate in human macrophages and induce apoptosis. Incubation of freshly added uninfected autologous macrophages with apoptotic M. avium-infected macrophages results in 90% inhibition of bacterial growth. Apoptosis also prevents the release of intracellular components and the spread of mycobacterial infection by sequestering the pathogens within apoptotic bodies. Consistent with the model that host cell apoptosis is a defense mechanism against mycobacteria is the finding that the virulent M. tuberculosis strain H37Rv induces substantially less macrophage apoptosis than the attenuated strain H37Ra. Evasion of apoptosis by this pathogen is achieved by enhanced release of sTNFR2 by H37Rv-infected macrophages and subsequent formation of inactive TNF-alpha-TNFR2 complexes. These observations contribute to the hypothesis that apoptosis of the host macrophage is an important defense mechanism in mycobacterial infections, which prevents the spread of the infection.

Regulation of human cytotoxic T lymphocytes development by the synergistic effect of IL-7 and sCD23.

The present study was undertaken to investigate the interaction of IL-7 and sCD23 on human peripheral blood T cell activation and CTL differentiation. Purified T lymphocytes were stimulated with mitogen plus IL-2 and subcultured for 7 days with IL-7 and/or sCD23. The combination of IL-7 and sCD23 synergistically enhanced the proliferation of both CD4+ and CD8+. T cells. CD8+ T cells, however, were usually more responsive to IL-7 and sCD23. This synergy was observed on both subsets of T cells. Furthermore, these cytokines synergistically augment the CTL activity of CD8+ T cells in both mitogen- and antigen-activated T cells. MAbs anti-IL-2 or anti-IL-2R (CD25) and anti-IL-12 had no effect on T cell proliferation and CD8+ cytotoxic activity induced by IL-7 and sCD23. We analyzed the effect on IFN-gamma induction by CD8+ T cells and found that IL-7 alone was incapable of inducing detectable levels of IFN-gamma production, but together with sCD23 it enhanced the production of IFN-gamma. We also found that IFN-gamma was not required for enhanced CTL activity of CD8+ T cells, because rabbit anti-IFN-gamma did not block the synergistic effects of either cytokine. The data demonstrate that the synergistic stimulatory activity of IL-7 and sCD23 may be of significance in the human CTL development and provide an alternative mechanism of stimulating T cells for use in immunotherapy.

Modulation of TCR usage in HIV-1 infection is regulated by IL-7 and sCD23.

The purpose of this study is to elucidate the effect of interleukin-7 (IL-7) and soluble CD23 (sCD23) on Phorbol12 Myristate13 Acetate (PMA) activated CD4+ TCR alpha beta+ cells of HIV-1 infected subjects. CD23 and IL-7R were detectable on activated CD4+ T cells of these subjects by FACS. Addition on IL-7 (1000 U/ml), at the onset of cultures, resulted in a significant increase of CD23 expression. We also demonstrated that T cells proliferation and CD23 expression in the presence of exogenous IL-7 occur in an IL-2 independent manner. Addition of IL-7 and sCD23 to activated CD4+ cells of HIV-1 infected subjects induced a proliferative response of TCR alpha beta cells. In contrast, addition of either sCD23 or IL-7 to activated CD4+ T cells did not result in an increase of TCR alpha beta expression. The data provide direct evidence that sCD23 in combination with IL-7 induce proliferation of activated CD4+ T cells of HIV-1 infected subjects to augment TCR alpha beta expression. These results support the possibility that IL-7 plus sCD23 might play an important role in the modulation of TCR alpha beta expression in HIV infection.

Interleukin 7 and sCD23 synergize in the induction of human T cell activation in HIV-1-infected subjects.

The role played by CD23 in retroviral infections is still unclear. The synergistic effects of interleukin 7 (IL-7) and sCD23 on T cell proliferation and the generation of HIV-1-specific cytotoxic T lymphocytes (CTL) in mitogen- and antigen-stimulated systems were examined. Addition of IL-7 and sCD23 at the onset of culture resulted in a marked augmentation of T cell proliferation and cytotoxic activity. Studies of CTL development in purified mitogen CD8+ T cells demonstrated that IL-7 and sCD23 could act directly on the CD8+ lymphocyte subset to augment cytotoxicity. The data demonstrate that IL-7 and sCD23 synergistically augmented CTL activity independently of IL-2 and IL-12. We analyzed the effects on IFN-gamma production by CD8+ T cells and found that IL-7 alone did not induce detectable levels of IFN-gamma production, but together with sCD23, it synergistically enhanced the production of IFN-gamma. We also found that IFN-gamma appeared not to be required for the enhanced CD8+ CTL activity because rabbit anti-IFN-gamma antibody did not block the synergistic effects of IL-7 and sCD23. These results indicate that IL-7 and sCD23 can exert major upregulatory effects on human CTL development and suggest that these effects are both proliferative and differentiative.

Interleukin-7 modulates CD23 and HLA-DR expression on CD4+ T cells and promotes a Th-2 type citokine profile.

The expression of CD23 on PHA-activated human PBT (peripheral blood T) cells of healthy donors was investigated. It appears that CD23 is expressed solely on activated CD4+ T cells. Cytofluorotometric analysis revealed that 6% of PHA-activated CD4+ T cells expressed CD23, while unstimulated CD4+ T cells express no detectable CD23. The addition of IL-7 (1000 U/ml) to activated CD4+ T cells resulted in a marked augmentation of CD23 expression (29%). CD23 expression was blocked by M20 and M26 mAbs, but no reduction was detected by anti-IL-2R (CD25) mAb. This suggests that IL-7 has a specific regulatory effect on CD23 expression independent of IL-2. Northern Blot analysis showed a marked increase of CD23 mRNA detected in PHA-activated CD4+ T cells plus IL-7. IL-7 was also able to upregulate the expression of HLA-DR on activated CD4+ T cells. Optimal HLA-DR and CD23 induction by IL-7 occurred at 48 and 72 h of culture. The addition of CHX revealed that the induction of CD23 and HLA-DR by IL-7 required intact protein synthesis. Furthermore, PHA activated CD4+ T cells cultured in the presence of IL-7 are polarized to a Th-2 pattern of cytokine production.

Programmed cell death of Mycobacterium avium serovar 4-infected human macrophages prevents the mycobacteria from spreading and induces mycobacterial growth inhibition by freshly added, uninfected macrophages.

Mycobacterium avium, an opportunistic pathogen in AIDS patients, replicates in human macrophages (Mphi) and induces programmed cell death (PCD). In this study we examine the effect of freshly added, uninfected Mphi on M. avium growth in apoptotic Mphi cultures. Incubation of uninfected autologous Mphi with apoptotic Mphi infected with M. avium for 6 h results in 90% inhibition of bacterial growth. The uninfected Mphi adhere to M. avium-infected apoptotic, but not to nonapoptotic M. avium-infected Mphi, suggesting a specific interaction between apoptotic and nonapoptotic Mphi. PCD of the host Mphi also prevents the release of intracellular components and the spread of the mycobacterial infection. Once the apoptotic infected Mphi reach the necrotic stage, mycobacteria and other intracellular material are released; the latter suffice to support extracellular mycobacterial replication. Necrosis of M. avium-infected Mphi is significantly augmented by the transglutaminase inhibitors dansyl-cadaverine and cystamine, indicating that apoptosis of Mphi is dependent on the extent of cross-linking of cell proteins by transglutaminases. Consequently, transglutaminase inhibitors accelerate the release of mycobacteria and intracellular components from the infected Mphi into the medium. These findings indicate that PCD of M. avium-infected Mphi is an important defense mechanism, preventing the spread of infection by sequestering the mycobacteria and by contributing to their demise by activation of newly recruited uninfected Mphi.

A new role for interleukin-7 in the induction of LFA-1 and VLA-4 adhesion molecules in Phorbol 12myristate 13acetate activated CD4+ CD23+ T-cell subset.

BACKGROUND: The low affinity receptor for IgE, CD23, has been described in several pathological conditions. However, the factors involved in the upregulation or downregulation of this receptor are still debated. METHODS AND RESULTS: We studied the effect of interleukin 7 (IL-7) on the expression of CD23 in normal PBT cells stimulated with PMA + Ca2. The data indicate that activated PB-T cultured in the presence of IL-7 showed an increased expression of CD23. The induction of IL-7 on CD23 production appears to be independent of IL-2, IL-4, IL-9, IL-15. Indeed, the addition of specific MoAbs anti-IL-2, IL-4, IL-9, IL-15 or anti-IL2R was unable to block the effect of IL-7 on CD23. The addition of IL-7 to a specific subset CD4+ CD23+ was able to augment the adhesiveness of T cells to parenchymal cell monalayers. The use of different cytokine (IL-2, IL-4, IL-9, IL-15) resulted in no increase of adhesiveness. In contrast the addition of IL-7 to a different T-cell subset (i.e. CD4+ CD23-) was unable to rescue the lack of adhesiveness observed in these cells. Blocking experiments with MHM6 MoAb were able to drastically reduce the adhesiveness observed in CD4+ CD23+ subsets. The presence of LFA-1 and VLA-4 adhesion molecules were responsible for the augmented adhesiveness of activated CD4+ CD23+ T cells cultured in the presence of IL-7. Blocking experiments with anti-LFA-1, VLA-4, anti-LFA-1beta plus VLA-4alpha MoAbs or anti-ICAM-1 MoAb added to the monolayers resulted in a complete inhibition of adhesion to parenchymal monolayers. In contrast, the addition of anti-IL-7 or anti-IL-7R MoAbs were able to block the augmented adhesiveness of CD4+ CD23+ cells to monolayers observed in the presence of IL-7. CONCLUSION: Taken together these findings point to the likelihood that IL-7 is responsible for the observed quantitative difference in the level of adhesion molecules and may open a new role of CD23 in the immune regulation.

Interleukin-7 modulates intracytoplasmatic CD23 production and induces adhesion molecule expression and adhesiveness in activated CD4+CD23+ T cell subsets.

The low-affinity receptor for IgE, CD23, has been described in several pathological conditions. However, the factors involved in the upregulation or downregulation of this receptor are still debated. We studied the effect of interleukin 7 (IL-7) on the production of CD23 in normal PBT cells stimulated with PMA + Ca2. The results demonstrate that cytoplasmic CD23 level was significantly augmented by costimulation with PMA + Ca2 plus IL-7 (1000 U/ml). Using an intracytoplamatic cytometric analysis, an accumulation of intracellular CD23 was observed at 48 hr in the presence of IL-7. This appears to have a profile different from the CD23 surface expression peaking at 72 hr of culture. We were also able to show that sCD23 was specifically increased by IL-7 and occurred with an early peak at 72 hr and a late peak at 120 hr of culture. The increased release and the biphasic production of sCD23 may reside in an accelerated degradation of the receptor due to an excessive accumulation of it. Restimulation of CD4+ T cells with PMA + Ca2 without IL-7 changed the profile of sCD23 production showing a second peak at 144 hr of culture. The induction of IL-7 on CD23 production appears to be independent of IL-2, IL-4, IL-9, and IL-15. Indeed, the addition of specific mAbs anti-IL-2, -IL-4, -IL-9, -IL-15, or anti-IL-2R was unable to block the effect of IL-7 on CD23. The addition of IL-7 to specific subset CD4+CD23+ was able to augment the adhesiveness of T cells to parenchymal cell monolayers. The use of different cytokine (IL-2, IL-4, IL-9, IL-15) resulted in no increase of adhesiveness. In contrast, the addition of IL-7 to a different T cell subset (i.e., CD4+CD23-) was unable to rescue the lack of adhesiveness observed in these cells. The adhesion molecules LFA-1 and VLA-4 were responsible for the augmented adhesiveness of activated CD4+CD23+ T cells cultured in the presence of IL-7. Blocking experiments with anti-LFA-1beta, VLA-4alpha, anti-LFA-1beta plus VLA-4alpha mAbs, or anti-ICAM-1 mAb added to the monolayers resulted in a complete inhibition of adhesion to parenchymal monolayers. In contrast, the addition of anti-IL-7 or anti-IL-7R mAbs was able to block the augmented adhesiveness of CD4+CD23+ cells to monolayers observed in the presence of IL-7. A significant augmentation of LFA-1 and VLA-4 was observed in cells cultured in the presence of IL-7. Taken together these findings point to the likelihood that IL-7 is responsible for the observed quantitative difference in the level of adhesion molecules and may open a new role of CD23 in the immune regulations.

CD23 expression in activated human T cells is enhanced by interleukin-7.

Despite evidence for the expression of the low-affinity Fc receptor for IgE (Fc epsilon RII/CD23) in several pathological conditions, the role played by CD23 in normal human T cells is still unclear. We studied the effect of a stomal-derived cytokine, interleukin (IL-7), on the expression of CD23 in human T cells stimulated with 10 micrograms/ml phytohemagglutinin (PHA). The results demonstrate that IL-7 did not induce CD23 expression in the resting T cells. However, PHA-induced CD23 expression was enhanced by costimulation with IL-7 (1,000 U/ml). Cytofluorometric analysis revealed that CD23 expression in activated T cells was enhanced by the addition of IL-7 (from 2% to 18%). It was also observed that the effect of IL-7 on CD23 expression is exclusively on CD4+ T cells. The enhanced expression of CD23 was blocked by an anti-IL-7 monoclonal antibody (mAb), but not by IL-2 and IL-4 mAbs. This suggests that IL-7 is a potent regulatory cytokine capable of acting independently of IL-2 and IL-4 in the expression of CD23. Northern blot analysis showed an increase in CD23 mRNA when activated T cells were cultured in the presence of IL-7. A significant increase in receptor numbers on activated T cells was detected by Scatchard analysis when IL-7 was added to the cell cultures. The induction of CD23 expression by IL-1, IL-3, IL-4, IL-5, IL-6, interferon-8 and OKT3 on PHA-activated T cells was not of the same magnitude as observed in the presence of IL-7. These results demonstrate a selective induction of CD23 expression on activated human T cells cultured in the presence of IL-7. These data indicate that the stromal-derived growth factor points to an important role of CD23 in the regulatory network of the immune response.

Animal models for perinatal transmission of pathogenic viruses.

In earlier work, mouse models have been used to demonstrate the efficacy and lack of toxicity of transplacental and perinatal AZT therapy. These practical small animal models can be useful for evaluating antiviral drugs aimed at common retroviral functions only, since Type C MuLVs are used. A primate model for fetal infection with an immunosuppressive lentivirus, SIV, has been established using ultrasound-guided inoculation of the amniotic fluid. The infection rate was 86% overall and 100% if the fetal SIV exposure occurred at least 19 days before delivery. The suspected major route of vertical HIV-1 transmission, that is, virus entry through fetal mucous membranes or skin, is replicated by our approach. The high fetal infection rate will allow studies of SIV pathogenesis during various stages of fetal development. This model should be well suited to development and evaluation of therapeutic strategies for preventing fetal infection.

Simian immunodeficiency virus infection via amniotic fluid: a model to study fetal immunopathogenesis and prophylaxis.

The rising prevalence of infection with the human immunodeficiency virus type 1 (HIV-1) in young women will increase the number of infected children worldwide. Because HIV-1 seems to be transmitted mostly intrapartum, fetal infection probably occurs mainly via skin or mucous membrane exposure. A model for this route of fetal infection has been established in primates. After injecting the simian immunodeficiency virus (SIV) into amniotic fluid during late gestation, six of seven rhesus monkeys were born infected. All infected neonates were viable and showed signs of disease, such as low birth weights, lymphadenopathy, and rashes. Cytotoxic T-cell responses to SIV were absent in neonates, but present in mothers. The high fetal infection rate allows studies of lentiviral immunopathogenesis during ontogeny and the development of strategies to prevent maternal HIV-1 transmission.

CD23/Fc epsilon RII expression on phytohemagglutinin-A- or phorbol-12myristate-13acetate-Ca(2+)-activated human tonsil T cells.

The low-affinity Fc receptor for IgE, CD23/Fc epsilon RII, has been expressed in T cell lines and pathologic T cells, but its presence on normal human T cells is still debated. We studied the expression of CD23/Fc epsilon RII on purified T cells from normal peripheral blood mononuclear cells (PBMC) or tonsil T cells stimulated with 10 micrograms/ml phytohemagglutinin A (PHA) or phorbol-12myristate- 13acetate (PMA) Ca2+. Using two-dimensional flow cytometry, the tonsil T-cell-enriched population showed > 10% of CD23/Fc epsilon RII expression when coexpressed with the CD3 antigen. CD4+ T cells appear to be principally involved in the expression of CD23/Fc epsilon RII, although we were unable to detect a clear expression of CD23/Fc epsilon RII in PBMC that were activated with either PHA or PMA Ca2+. PHA stimulation resulted in the release of IgE binding factor (IgEBF). The induction of CD23/Fc epsilon RII expression in PHA- and PMA-Ca(2+)-activated T cells was enhanced by IL-4, but not by IgE or IL-6. IL-4 also augmented the PHA- and PMA-Ca(2+)-induced release of IgEBF. The addition of supernatant from the Epstein-Barr virus (EBV)-infected cell line to PHA- or PMA-Ca(2+)-stimulated tonsil T cells did not increase CD23/Fc epsilon RII expression. The expression of CD23/Fc epsilon RII mRNA was detected in RNA prepared from a tonsil T-cell-enriched population by Northern blot analysis.

Detection of IgG subclasses with anti-IgE activity in patients with atopic diseases.

Significantly increased levels of IgG anti-IgE were seen in atopic patients as compared with controls. A correlation was observed between the levels of anti-IgE autoantibodies and serum IgE in the groups of atopic patients studied. No significant correlation was found between IgG anti-IgE levels and severity of the disease or between IgG subclasses with anti-IgE activity and clinical status. Analysis of IgG subclasses with anti-IgE activity showed that IgG1 and IgG4 were clearly factors in differentiating the atopics from the controls. IgG2 and IgG3 anti-IgE levels were not statistically significantly elevated. The lack of these autoantibodies may be explained by the presence of immune complexes or the lack of specificity of the monoclonal antibodies used in this study. These observations have not yet determined whether these autoantibodies and the isotypic selection and restriction observed play a role in the dysregulation of the immune response and in the evolution towards atopy.

Characterization of new rat anti-mouse IgE monoclonals and their use along with chimeric IgE to further define the site that interacts with Fc epsilon RII and Fc epsilon RI.

Three rat monoclonal antibodies specific for mouse IgE (C12B9, 23G3, and B1E3) were established by using monoclonal anti-DNP mouse IgE (mIgE) as immunogen. These antibodies, as well as a fourth, (R1E4) were characterized. It was found that one antibody (C12B9) recognizes an allotypic determinant (Igh-7a) found on the C epsilon chain of mIgE. Antibody cross-blocking studies and epitope mapping studies using recombinant mIgE indicated that 3 antibodies (C12B9, R1E4 and 23G3) were directed against the C epsilon 3 domain while one (B1E3) was directed against the C epsilon 4 domain. A highly specific sandwich RIA for mIgE was developed using these antibodies. Use of these monoclonal anti-mIgE antibodies in conjunction with recombinant chimeric mIgE-human IgG1 molecules, demonstrated that the C epsilon 3 domain is important in the binding of mIgE to the murine B cell Fc epsilon RII as well as to the murine mast cell F epsilon RI. The presence of the C epsilon 4 domain influenced the binding of the recombinant IgE to the Fc epsilon RII; in contrast to the C epsilon 4 domain had no effect on binding to the Fc epsilon RI.

Evidence for IgE immune complexes and distribution of IgG subclasses with anti-IgE activity in patients with atopic dermatitis.

The anti-IgE autoantibody was detected, using a radioimmunoassay, in 17 out of 35 (48.6%) of patients with atopic dermatitis. Significant increased levels of IgG-anti-IgE were seen in the patients studied compared with the control group. The specificity of the anti-IgE autoantibody was confirmed by competitive inhibition assay using IgG, IgM, IgE myeloma. A correlation was observed between the levels of IgG-anti-IgE and serum IgE but not between the IgG subclasses with anti-IgE activity and the clinical status. These data demonstrate that the IgG subclass distribution with anti-IgE activity belongs mostly to the IgG1 and IgG4 subclasses compared with the controls. Moreover, ultracentrifugation analysis indicated that the IgG-anti-IgE in the serum samples from the patients with atopic dermatitis was present in the form of an immune complex with self-IgE. These observations may suggest that the anti-IgE complexes may play a broader role in the modulation of the immune response and that this autoantibody may mask recognition of IgE in conventional assays.

Complement activation is associated with the presence of specific human immunodeficiency virus (HIV)-anti-HIV immune complexes in patients with acquired immunodeficiency syndrome-related complex or lymphoadenopathy syndrome.

The complement system was examined in a group of eight patients (six with lymphoadenopathy syndrome (LAS); two with acquired immunodeficiency syndrome (AIDS)-related complex (ARC], who were found to be human immunodeficiency virus (HIV)-positive, for the presence of specific HIV-anti-HIV complexes. A significant impairment of the classical and/or alternative pathway was found associated with the presence of cleavage fragments of C3 and/or B and a significant reduction in the complement factors studied. Ultracentrifugation fractions of serum samples obtained from one of the patients were assessed for the detection of specific HIV-anti-HIV (GP41-anti-GP41) complexes and were incubated with normal human serum to determine their complement activation capacity. A clear complement activation was found with the fraction in which a clear peak of HIV-anti-HIV (GP41-anti-GP41) immune complexes was present. The results demonstrate that specific immune complexes and complement activation are sometimes concomitantly present in patients with AIDS-related disease and that specific immune complexes may be one of the causal factors of the pathogenesis of complement activation in these patients. Possible consequences for the severe immune regulation with relevance to the dramatic failure in treating the virus effectively are discussed.

Interleukin-2, interleukin-2 receptor and gamma-interferon synthesis by peripheral blood mononuclear cells in chronic hepatitis delta virus infection.

The behaviour of the immune system during liver damage caused by chronic hepatitis delta virus (HDV) infection was evaluated by assessing, in 16 patients with HBsAg+ chronic liver disease and HDV superinfection (15 HBeAg-, 1 HBeAg+), phytohaemagglutinin (PHA)-induced interleukin-2 synthesis and interleukin-2 receptor expression, PHA and staphylococcal enterotoxin B (SEB)-induced gamma-interferon synthesis and, in some cases, the presence of hepatitis B virus DNA (HBV-DNA) within peripheral blood mononuclear cells (PBMC). The results were compared to those obtained in 13 patients without HBV replication (i.e., serum HBV-DNA and liver HBcAg-negative), in 15 with HBV replication (i.e., serum HBV-DNA and/or liver HBcAg-positive) with chronic liver disease without HDV superinfection, and in 15 HBsAg-negative healthy control subjects. The lymphokine pattern in HDV infection was comparable to that of healthy subjects and of HBV non-replicating patients without HDV superinfection. Interleukin-2 receptor expression and gamma-interferon synthesis were however significantly decreased in HDV-negative patients with active HBV replication. HBV-DNA was detected in PBMC from 8 of 23 patients, without any correlation with the lymphokine pattern. Our results suggest that in HDV-related chronic liver disease, immune system alterations are unlikely. HDV superinfection does not affect the occurrence of HBV-DNA sequences within the leukocytes. HBV-DNA in PBMC does not interfere with the interleukin-2 system nor with the gamma-interferon response in HBV- and HDV-related chronic liver disease.

IgG autoantibody to IgE in atopic patients.

An IgG type of antibody directed against IgE has been studied in serum from healthy and allergic individuals. The technique used is based on a solid phase paper radioimmunoassay in which the discs were sensitized with purified IgE myeloma. After incubation with patients' serum, human IgG labeled with iodine 125 was added. The anti-IgE antibodies were partially blocked by endogenous IgE in the serum and heating the serum samples at 56 degrees C disrupted the immune complexes (ie, IgG-aIgE:IgE), thereby increasing the detectable levels of IgG anti-IgE. The specificity of anti-IgE autoantibody was confirmed by both competitive inhibition and absorption experiments, using IgG, IgM, IgA, IgE, and rabbit anti-human IgG. Significantly raised levels of anti-IgE autoantibody were found in patients suffering from atopic disorders in comparison to the controls. These observations may suggest that the anti-IgE autoantibody could play a certain role in the modulation of IgE-mediated immune system and the pathogenesis of atopic diseases.