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Biomedical subjects

H G Durkin

Publications and source records attributed to H G Durkin.

At least 19 recordsLinked to original sources
PubMed2001

Increased expression of CD23 (Fc(epsilon) receptor II) by peripheral blood monocytes of aids patients.

Monocytes expressing the Fcepsilon receptor II (CD23) play important roles in inflammatory and allergic immune responses. We found that peripheral blood monocytes of AIDS patients express increased levels of CD23, compared with monocytes of healthy HIV-1-seronegative individuals (controls) (p < 0.05). We compared expression of monocyte CD23 with expression of monocyte Fcgamma receptors (CD16, CD32, CD64), plasma/serum levels of IgE (also IgM, IgG, IgA), and Th1 (IFN-gamma) and Th2 (IL-4, IL-10) cytokines. We found that monocyte CD23 expression directly correlated with monocyte CD16 expression (p < 0.01, R = 0.58), which was also increased in AIDS patients; there was no correlation with CD32 or CD64 or with soluble factors in plasma/serum (i.e., IgE, IL-4, IL-10, and IFN-gamma). Interestingly, despite the known ability of IL-10 to downregulate monocyte CD23 expression, plasma IL-10 levels were increased in these AIDS patients compared with controls (p < 0.05). We thus evaluated the effect of AIDS and control plasma or rhIL-10 to regulate CD23 expression by monocytes in cultures (24 hr) of healthy human cells +/- treatment with anti-IL-10R blocking antibody. We found that anti-IL-10R blocking antibody treatment had no effect on monocyte CD23 expression in cultures containing AIDS plasma, but increased monocyte CD23 expression in cultures containing control plasma (p < 0.05) or rhIL-10. In conclusion, the identification of increased monocyte CD23 expression in AIDS patients may further characterize the aberrant activated phenotype of monocytes during the immunopathogenesis of HIV-1 disease. Further, monocyte CD23 expression does not appear to be suppressed by the IL-10-enriched environment in AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Thymus and tolerance. Is regulation the major function of the thymus?

This paper will serve as a contribution to the current reassessment of the relative roles of clonal selection and regulation in specific immunologic tolerance. We review basic studies in the Waksman laboratory that first established the importance of the thymus in tolerance and the possible contribution of regulatory cells generated in the thymus to self-tolerance. Experimental evidence is presented to suggest that there exists a wide range of immunoregulatory mechanisms, many of which deserve more intensive investigation in relation to the tolerance question. These include regulation based on idiotype-specific recognition, multiple forms of immune deviation, two well-described and quite distinct forms of T-cell receptor alphabeta "suppressor cell", and several regulatory systems involving multiple cells acting in concert. We do not comment on more recently described regulatory cells, such as certain gammadelta T-cell subsets, natural killer T cells, CD4-CD8- T cells, and others. Basic studies in our laboratory and in other laboratories pointed to antigen-presenting cells (APC) generated in the thymus as possible mediators of tolerance. Certain cytokines, first described in our laboratory, including lymphotoxin and the "inhibitor of DNA synthesis" produced by T cells and interleukin-1 produced by macrophages, also may act as significant components of regulatory systems. The rapid entry of exogenous and self-antigens into the thymus and the free migration of specific regulatory T cells and of APC in both directions between thymus and periphery are also stressed.

Animals↗
PubMed1999

Cytokine profile of a long-term pediatric HIV survivor with hyper-IgE syndrome and a normal CD4 T-cell count.

BACKGROUND: An elevated IgE level and increased production of T(H2) cytokines are factors associated with poor prognosis in HIV infection. We report a pediatric long-term survivor of vertically acquired HIV infection with a normal CD4 count and a low viral burden despite the lack of antiretroviral therapy and a phenotype resembling hyper-IgE syndrome. OBJECTIVE: We sought to characterize the patient's T(H1) versus T(H2) cytokine profile and anti-HIV-specific immune responses. METHODS: Supernatants collected from cultures of peripheral blood T cells stimulated with phorbol myristate acetate plus ionomycin were assayed for T(H1) and T(H2) cytokines by means of ELISA. Specific IgE antibodies were determined by immunoblot. HIV-specific cytotoxic T-lymphocyte responses were measured from cell lysis by fresh T cells of autologous B-lymphoblastoid cells expressing recombinant HIV proteins. RESULTS: Patient CD4(+) T cells secreted significantly more T(H2) cytokines, IL-4 (P <.003) and IL-5 (P <.03), than HIV-infected and seronegative control cells. No difference was noted in T(H1) cytokine production. IgE specific for HIV gp160, p24, p17, and p66 proteins and Aspergillus fumigatus was detected in patient sera. Despite predominance of T(H2) cytokines, HIV-specific cytotoxic T-lymphocyte activity was vigorous. CONCLUSIONS: The patient demonstrated predominantly T(H2) cytokine production in vitro. Unlike other patients with HIV who have hyper-IgE and increased T(H2) cytokine production, our patient has maintained HIV-specific immune responses, a low viral load, and a normal CD4 count without antiretroviral therapy. These findings support a diagnosis of primary hyper-IgE syndrome. Presence of anti-HIV-specific IgE may represent a protective mechanism against HIV replication in our patient.

CD4 Lymphocyte Count↗
PubMed1998

Altered levels of urokinase on monocytes and in serum of children with AIDS; effects on lymphocyte activation and surface marker expression.

Urokinase (UK) type plasminogen activator is a serine protease produced by activated human monocytes. Despite the well-documented roles played by UK in cell-mediated immunity in healthy humans, the roles played by UK in the derangements of cell-mediated immune responses observed in HIV disease remain largely undefined. In these studies the numbers of peripheral blood lymphocytes and monocytes bearing surface UK (UK+) as well as serum levels of UK (flow microfluorimetry and ELISA, respectively) were determined in children with AIDS and in healthy HIV-negative children. The effects of exogenous UK on lymphocyte activation (cell cycle analysis using living cells) and surface marker (CD3, CD4, CD8, and CD19) expression (flow microfluorimetry using fixed cells) were also studied. Data are expressed as percent total cells. Numbers of UK+ lymphocytes in children with AIDS were similar to those observed in healthy children. In contrast, numbers of UK+ peripheral blood monocytes were dramatically decreased (> 70%) in the children with AIDS. However, serum levels of UK were increased (nearly threefold) in these children. When lymphocytes from these children were cultured with soluble UK, numbers of cells in S phase of cell cycle appeared suppressed. Incubation of fixed lymphocytes from either a child with AIDS or from a healthy child with exogenous UK appeared to increase numbers of cells expressing CD3. Incubation with UK had no effect on expression of any other surface marker (CD4, CD8, or CD19) using cells from the child with AIDS. In contrast, incubation with UK appeared to decrease (fivefold) numbers of cells expressing CD19 and increase numbers of cells expressing CD4 and CD8 only when fixed lymphocytes from a healthy HIV-negative child were used. The results suggest important roles for UK in regulation of lymphocyte surface markers in general and in CD3- and CD19-dependent lymphocyte activation pathways specifically. Furthermore, these studies add to a widening body of evidence implicating UK dysregulation in the pathogenesis of HIV disease and may point to pharmacological opportunities involving UK to delay or prevent progression of HIV infection into full-blown AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1997

IgE-bearing cells and epsilon-specific mRNA in lymphoid organs of two children with AIDS.

To characterize the cellular basis of IgE responses in HIV-positive (HIV+) children, we obtained central (bone marrow [BM], thymus) and peripheral (Peyer's patches [PP], mesenteric [MLN], and other lymph nodes [OLN], spleen), lymphoid organs from two children with AIDS (females, 2 and 8 years old), and from a non-HIV-infected trauma victim (female, 5 years old) at autopsy. PP were obtained from one of the HIV+ children (2 yr old) and from the non-infected child, but no PP were detected in small intestine of the 8-yr-old HIV+ child. Numbers of lymphocytes bearing surface IgE, CD19, CD3, CD4, and CD8 in lymphoid organs were determined (flow cytometry) and evaluated for expression of epsilon-specific (E) mRNA (RT-PCR). Thymus and MLN of the HIV+ child without PP contained high numbers of IgE+ (34% and 41%, respectively) and CD19+ (32% and 28%, respectively) cells; IgE+ cells were not found in any other organ. In contrast, in the HIV+ child with PP, IgE+ cells were detected in all organs, except BM. The thymus of this child contained fewer CD19+ cells (7%). However, in both HIV+ children, all lymphoid organs, including thymus, contained E mRNA. Because numbers of IgE+ cells often far exceeded numbers of CD19+ B cells, and because CD8+ T cells predominated in all organs, some of the IgE+ cells were probably CD8+ T cells with cytophilic IgE and may include IgE-specific regulatory and/or memory T cells. IgE responses were not detected in the healthy trauma victim nor were B cells found in thymus. The data suggest that during HIV infection, IgE+ B cells may be found in thymus and that synthesis of IgE may occur in all lymphoid organs except BM.

Acquired Immunodeficiency Syndrome↗
PubMed1996

IFN-alpha-mediated suppression of low-affinity FC(epsilon) receptors on Peyer's patch lymphocytes and augmentation of soluble CD23: implications for IgE responses.

The ability of interleukin (IL)-6 or interferon-alpha (IFN-alpha) to regulate expression of low-affinity Fc(epsilon) receptor (CD23) and serum levels of CD23 was studied in benzylpenicilloyl-keyhole limpet hemocyanin-sensitized BALB/c mice at the peak of a hapten-specific immunoglobulin E (IgE) antibody-forming cell (AFC) response. These responses are analogous to those observed in human atopic disease. To induce peak IgE responses, mice were injected intraperitoneally with BPO-KLH (10 micrograms) in aluminum hydroxide gel (alum) on days 0, 21, and 42. On day 44, mice were injected subcutaneously with IL-6 (100-1000 U) or IFN-alpha (1000-10,000 U). On day 46, numbers of CD23+ lymphocytes in Peyer's patches (PP), mesenteric lymph nodes (MLN), and spleen and levels of soluble CD23 in serum were determined (flow microfluorimetry and enzyme-linked immunosorbent assay, confirmed by competition assay). Data are expressed as percent total cells or as optical density at 490 nm. IFN-alpha treatment strongly suppressed (up to 100%) numbers of CD23+ cells exclusively in PP (i.e., numbers of CD23+ cells in MLN and spleen were unchanged) whereas serum levels of soluble CD23 were dramatically increased (60%). IL-6 treatment had no effect on either numbers of CD23+ lymphocytes or on serum levels of soluble CD23. The data suggest that the mechanism(s) by which IFN-alpha, but not IL-6, regulates IgE responses involves suppression of CD23 expression on lymphocytes in PPs and supports a central role for these organs in regulation of IgE responses in vivo.

Animals↗
PubMed1996

IgE against HIV proteins in clinically healthy children with HIV disease.

Elevated serum Ige was detected in 26% (7 of 30) of children with HIV infection. The majority of children with elevated IgE were of one ethnic group (Puerto Rican) (4 of 7), compared with only 9% (2 of 23) in the normal to low IgE group (p = 0.02). Most of the children with elevated IgE had decreased circulating CD4+ T cells (5 of 7 or 71%); but none had opportunistic infections, and none failed to thrive. Although similar numbers of children with normal to low IgE had decreased circulating CD4+ T cells (19 of 23 or 83%), this group had opportunistic infections (6 of 23 or 26%) and failure to thrive (7 of 30 or 30%). There was no difference in incidence of allergic symptoms between groups. IgE antibody against HIV protein was detected by Western blot technique in the sera of three children with elevated serum IgE. Thus we have identified a group of children with HIV infection and elevated serum IgE of predominantly one ethnic group, who are without opportunistic infections or failure to thrive, some of whom produce HIV-specific IgE. This suggests that IgE may play a protective (perhaps late compensatory) role in HIV disease in genetically predisposed individuals.

AIDS-Related Opportunistic Infections↗
PubMed1995

Neuropeptide-mediated regulation of hapten-specific IgE responses in mice. I. Substance P-mediated isotype-specific suppression of BPO-specific IgE antibody-forming cell responses induced in vivo and in vitro.

The ability of substance P (SP) to regulate peak benzyl-penicilloyl (BPO)-specific IgE antibody-forming cell (AFC) responses in vivo and the ability of SP and other neuropeptides to regulate BPO-specific memory IgE AFC responses induced in vitro was determined. SP injected subcutaneously into BPO-keyhole limpet hemocyanin (BPO-KLH)-sensitized mice at the time of peak IgE responses suppressed these responses within 48 h (> 90%). The suppression obtained was IgE isotype-specific, dose-dependent, and transient. When spleen cells from immunized mice were cultured for 5 days with BPO-KLH, peak memory IgE AFC responses were induced in vitro. Inclusion of either SP or vasoactive intestinal peptide (VIP), but not neurotensin, serotonin, somatostatin, or gastrin, in cultures suppressed these responses in isotype-specific, dose-dependent fashion (approximately 70%). SP-, but not VIP-mediated suppression of IgE responses was abrogated by inclusion of anti-IFN gamma culture.

Animals↗
PubMed1994

Neuropeptide-mediated regulation of hapten-specific IgE responses in mice. II. Mechanisms of substance P-mediated isotype-specific suppression of BPO-specific IgE antibody-forming cell responses induced in vitro.

Previous studies in our laboratory have shown that substance P (SP), injected into benzylpenicilloyl-keyhole limpet hemocyanin (BPO-KLH) sensitized mice at the peak of the benzylpenicilloyl (BPO)-specific IgE response, suppressed these responses in isotype-specific fashion within 48 h. These studies also showed that SP, but not neurotensin (NT), serotonin (5-HT), somatostatin (SOM) or gastrin, suppressed BPO-specific memory IgE antibody-forming cell (AFC) responses induced in vitro, also in isotype-specific fashion. To investigate the mechanisms by which SP suppressed BPO-specific IgE AFC responses were induced in vitro, these responses were induced by culturing spleen cells from BPO-KLH sensitized mice for 5 days with BPO-KLH with or without whole SP, amino terminal SP (SP 1-4: Arg-Lys-Pro-Lys), or carboxy terminal SP (SP 8-11: Phe-Gly-Leu-Met). In some experiments, the SP receptor antagonist (D-Pro2, D-Phe7, D-Trp9)-SP (D-SP) was included in culture. In other experiments anti-interferon monoclonal antibody (anti-IFN gamma mAb) was in culture. Whole SP and SP 8-11, but not SP 1-4, suppressed BPO-specific IgE AFC responses induced in vitro. The suppression obtained was IgE isotype-specific and dose-dependent. Inclusion of SP receptor antagonist (D-Pro2, D-Phe7, D-Trp9)-SP inhibited suppression of BPO-specific memory IgE AFC responses by SP or SP 8-11. The SP-mediated suppression of BPO-specific memory IgE responses appeared to involve interferon gamma (IFN gamma).

Amino Acid Sequence↗
PubMed1994

IL-6 mediated isotype specific suppression of hapten specific IgE in serum of BPO-KLH sensitized mice: role of IFN alpha in maintainance of hapten specific IgE responses.

The ability of IL-6 or IFN alpha or antibodies to these cytokines to regulate serum levels of hapten specific immunoglobulins (IgM, IgG1, IgE, IgA) was studied in BPO-KLH (benzylpenicilloyl-keyhole limpet hemocyanin) sensitized BALB/c mice at the peak of a hapten specific IgE antibody forming cell (AFC) response. To induce peak IgE responses, mice were injected intraperitonealy (i.p.) with BPO-KLH (10 micrograms) in aluminum hydroxide gel (alum) on days 0, 21, and 42. On day 44, mice were injected s.c. with IL-6 (100-1000 U), IFN alpha (1000-10,000 U), anti-IL-6 (100-1000 neutralizing units [NU]), or anti-IFN alpha (1000-10,000 NU). On day 46, levels of BPO specific IgM, IgG1, IgE and IgA in serum were determined (ELISA). Data are expressed as micrograms/ml. IL-6 suppressed BPO specific IgE in serum in isotype specific fashion (to > 90%), increasing IgA (approximately 3 fold), and leaving IgM and IgG1 unchanged. Since removal of endogenous IL-6 with anti-IL-6 increased serum IgE, and suppressed IgG1 (approximately 50%), with IgM and IgA unchanged, this suggests that IL-6 is an isotype specific suppressor of peak IgE responses and as such may be useful in the therapeutic management of atopic disease. IFN alpha treatment increased serum IgE levels (60%), and potentiated IgA responses (> 30 fold), with IgM and IgG1 unchanged. Since removal of endogenous IFN alpha with anti-IFN alpha decreased IgE levels (approximately 50%), increasing IgA, with IgM and IgG1 unchanged, this suggests a role for IFN alpha as an isotype specific helper of peak IgE responses and in maintenance of IgA responses.

Animals↗
PubMed1993

Regulation of hapten-specific memory IgE responses induced in vitro. Requirement for both Thy-1+ AsGM1+ and Thy-1+ AsGM1- cells and for IFN-alpha and IL-4.

The roles of Thy-1+ and AsGM1+ spleen cells and cytokines (IL-4, IL-5, IL-6, IFN-alpha, and IFN-gamma) in regulation of hapten-specific memory IgE antibody-forming cell (AFC) responses induced in vitro were examined. BALB/c mice, injected i.p. with benzylpenicilloyl-keyhole limpet hemocyanin (BPO-KLH) (10 micrograms) on days 0 and 21, were killed on day 60 or day 120. Numbers of BPO-specific IgGI, IgE, and IgA AFC in spleen were determined by enzyme-linked immunosorbent spot assay after 0 to 6 days of culture +/- BPO-KLH. BPO-specific AFC of all isotypes were detected in spleen on day 60, but not on day 120. Day 60 AFC responses did not persist in culture in that no AFC were detected by day 2 of culture +/- BPO-KLH. When either day 60 or day 120 cells were cultured for 3 days with BPO-KLH, BPO-specific AFC responses were induced, and peaked on day 5, with similar numbers of AFC of each isotype induced with day 60 and day 120 cells. On day 60, spleen contained two subsets of Thy-1+ cells: AsGM1- (approximately 32% of total cells) and AsGM1+ (approximately 4%). Depletion and reconstitution experiments established that both subsets were required for induction of BPO-specific IgE AFC responses. Cytokines could not substitute for the Thy-1(+)-depleted cells. However, when unfractionated day 60 cells were cultured with cytokines or anti-cytokine antibodies, BPO-specific IgE AFC responses induced were both IFN-alpha and IL-4 dependent; either increased or decreased by IFN-gamma, depending on its concentration, and unaffected by IL-5 or IL-6.

Animals↗
PubMed1993

Suppression of human IgE antibody forming cell responses by IL-6.

To study the effects of cytokines on human IgE antibody forming cells (AFCs), log phase U266 myeloma cells (3 x 10(3)/ml), which secrete immunoglobulin E (IgE), were cultured for 0-24 h with and without cytokine or with or without antibodies against various cytokines. The numbers of IgE AFCs were determined in ELISPOT assay. We found that interleukin-6 (IL-6) suppressed (to 95%) whereas anti-IL-6 increased (to 148%) the numbers of IgE AFCs and that both worked in a dose-dependent fashion. IL-4 and interferon-gamma (IFN-gamma) also suppressed IgE AFC responses in a dose-dependent fashion. However, antibodies to these cytokines had no effect. In contrast, IFN-alpha increased (to fourfold) the numbers of IgE AFCs in a dose-dependent fashion. The data are the first to show a suppressive effect of IL-6 on human IgE responses and may also suggest a role for IL-6 in the treatment of atopic disease.

Antibody-Producing Cells↗
PubMed1993

Control of IgE responses. III. IL-6 and IFN-alpha are isotype-specific regulators of peak BPO-specific IgE antibody-forming cell responses in mice.

The ability of cytokines (IL-4, IL-5, IL-6, IFN-alpha, IFN-gamma, TNF-alpha, GmCSF) to regulate peak benzylpenicilloyl (BPO)-specific IgE antibody-forming cell (AFC) responses was investigated. These responses were induced in BALB/c mice by ip injection of BPO-keyhole limpet hemocyanin (BPO-KLH; 10 micrograms) in aluminum hydroxide gel on Days 0, 21, and 42. On Day 44, or on Days 43, 44, and 45, mice were injected sc with varying doses of cytokine or anti-cytokine antibody. On Day 46, the numbers of BPO-specific AFC (IgM, IgG1, IgE and IgA) in spleen were determined ex vivo in enzyme-linked immunosorbent spot assay. Among the cytokines tested, only IL-6 suppressed BPO-specific IgE AFC responses in an isotype-specific fashion (60-90%). However, treatment of mice with anti-IL-6 also suppressed these responses, suggesting that IL-6 can either suppress or increase peak antigen specific IgE responses, depending upon its concentration. Among the cytokines tested, only IFN-alpha increased BPO-specific IgE AFC responses in an isotype-specific fashion. Since treatment with anti-IFN-alpha suppressed these responses, it appears that IFN-alpha is required to maintain peak antigen-specific IgE AFC responses. IL-4 or IFN-gamma nonspecifically suppressed responses of all isotypes. Treatment with anti-IL-4 also suppressed IgE responses, suggesting that this cytokine is required to maintain peak antigen specific IgE responses. Treatment with anti-IFN-gamma increased IgE responses, indicating that IFN-gamma suppresses peak antigen-specific IgE responses.

Animals↗
PubMed1993

Control of IgE responses. 4. Isotype-specific suppression of peak BPO-specific IgE antibody-forming cell responses and of BPO-specific IgE in serum by muramyldipeptide or murabutide after administration to mice by gavage.

Muramyldipeptide (MDP) and murabutide (MB) suppressed hapten-specific IgE antibody-forming cell (AFC) responses in vivo. IgE responses were induced in BALB/c mice by intraperitoneal injection with benzylpenicilloyl-keyhole limpet hemocyanin (BPO-KLH) (10 micrograms) in aluminum hydroxide gel (Alum) on days 0, 21 and 42. On day 44, mice were fed (gavage) or injected subcutaneously with varying concentrations of MDP or MB (0.1-500 mg/kg). The mice were killed on days 45-70, and the numbers of BPO-specific IgM, IgG1, IgE, and IgA AFC in various lymphoid organs were determined in an enzyme-linked immunosorbent spot (ELISPOT) assay. In addition, levels of BPO-specific IgE in serum were determined by ELISA. Data are expressed as AFC/10(7) cells or as micrograms/ml. Feeding with MDP or MB on day 44 suppressed BPO-specific IgE AFC responses and serum levels of BPO-specific IgE within 48 h (day 46) (65-100% and approximately 50% decrease, respectively). With both molecules, the suppression was IgE isotype-specific, dose-dependent and transient. The suppression was also route-specific since it was obtained only when MDP or MB were given by gavage, and not when injected subcutaneously. These results show that peak antigen-specific IgE responses can be downregulated in vivo, in isotype-specific fashion, by a clearly defined class of molecules, MDP and MB, one of which, MB, is a candidate for clinical studies in man. The mechanism of suppression probably involves the modulation of gut-associated lymphoid tissue and mucosal immunity. The clinical implications are that pharmacologic agents of this type may be suitable for use in the therapeutic or prophylactic downregulation of IgE and, hence, in the therapy of IgE-mediated diseases in man such as allergic rhinitis, asthma, and other atopic diseases.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1993

Cytokine-induced suppression and potentiation of hapten-specific immediate hypersensitivity responses.

The ability of subcutaneously (s.c.) injected cytokines (IL-4, IL-5, IL-6, IFN alpha, IFN gamma, GMCSF) to regulate the induction of hapten-specific immediate hypersensitivity (IH) responses was studied in BPO-KLH (benzylpenicilloyl-keyhole limpet hemocyanin) sensitized BALB/c mice at the peak of a hapten-specific IgE antibody forming cell (AFC) response. To induce IH responses, mice were injected in the right pinna with either BPO-BSA (benzylpenicilloyl-bovine serum albumin), BPO-KLH (0.01-1.0 micrograms/ml) or mcAb anti-IgE (0.001 - 1.0 micrograms/ml); and in the left pinna with an equal volume of saline (0.05 ml). Pinnae were measured 5 min to 4 hr later using a micrometer caliper. Treatment of mice with IL-4 or IFN gamma dramatically suppressed the induction of IH responses in dose dependent fashion. In contrast, treatment of mice with IL-6 and IFN alpha increased these responses in dose dependent fashion, while GMCSF and IL-5 had no effect. The suppression obtained with IL-4 and IFN gamma, and the increases seen with IL-6 and IFN alpha, were transient since these cytokines, as well as GMCSF and IL-5, had no effect on IH responses elicited 21 days after the peak of BPO-specific IgE AFC responses. The data suggest that cytokine mediated effects on IH responses occur via changes in serum levels of BPO-specific IgG1 or IgE, through direct or indirect effects of cytokines on mast cells or other cell types, or by affecting the ability of BPO-specific homocytotropic antibodies to bind to mast cell surfaces.

Animals↗
PubMed1992

Origin and fate of IgE-bearing lymphocytes. II. Gut-associated lymphoid tissue as sites of first appearance of IgE-bearing B lymphocytes and hapten-specific IgE antibody-forming cells in mice immunized with benzylpenicilloyl-keyhole limpet hemocyanin by various routes: relation to asialo GM1 ganglioside+ cells and IgE/CD23 immune complexes.

The organs in which B cells bearing membrane-bound IgE (sIgE+) and benzylpenicilloyl (BPO)-specific IgE antibody-forming cells (AFC) first appeared were determined in BALB/c mice given BPO-keyhole limpet hemocyanin (10 micrograms) in aluminum hydroxide by various routes (i.p, gavage, s.c., i.v., or i.m.). In mice immunized by the i.p. route, the numbers and location of sIgE+ B cells and asialo GM1 ganglioside (AsGm1+) cells, the location of IgE/CD23 immune complexes, and the numbers of BPO-specific IgE AFC in lymphoid organs were determined. With all routes of immunization, no sIgE+ B cells or BPO-specific IgE AFC were ever detected in any organ before day 8. On day 8, with the s.c., i.v., or i.m. routes, sIgE+ B cells and IgE AFC appeared exclusively in Peyer's patches (PP); with the i.p. or gavage routes, sIgE+ B cells simultaneously appeared in both PP and mesenteric lymph nodes, whereas IgE AFC appeared only in PP. In mice immunized by the i.p. route, IgE/CD23 immune complexes and strikingly increased numbers of AsGm1+ cells transiently appeared only in PP after the appearance and preceding the "disappearance" of the sIgE+ B cells and IgE AFC. The data suggest that specific IgE responses originate in gut-associated lymphoid tissue and appear later in spleen. The data also associate the appearance of IgE/CD23 immune complexes and AsGm1+ cells with the "disappearance" of sIgE+ B cells and IgE AFC from PP.

Animals↗
PubMed1992

Constitutive production of PAI-II and increased surface expression of GM1 ganglioside by peripheral blood monocytes from patients with AIDS: evidence of monocyte activation in vivo.

To characterize the activation state of monocytes during human immunodeficiency virus (HIV) infection, peripheral blood monocytes (PBMs) from patients with acquired immunodeficiency syndrome (n = 10) and from healthy controls (n = 10) were cultured for 4 days. Monocyte culture supernatant (MCS) was collected daily, and levels of urokinase (UK) inhibitor PAI-II, a product of activated monocytes, released into MCS were determined (fibrin plate assay). To examine the activation state of PBMs independently, expression of GM1 ganglioside on PBMs from patients with AIDS (n = 9), patients with AIDS-related complex (ARC) (n = 8), HIV+ asymptomatic patients (n = 6), and HIV- healthy controls (n = 11) was determined (flow cytometry; living cells in suspension). Data are expressed as percent inhibition of UK, or as percent total cells. Patients' MCS collected on days 1-4 of culture contained similar levels of PAI-II because it inhibited UK in similar fashion (70-90%). In contrast, MCS from healthy controls, collected after 2 days, had decreased ability to inhibit UK (15-50%) and thus contained lower levels of PAI-II. Monocyte activation, measured by increased expression of GM1 ganglioside on PBM surfaces, directly correlated with the progression of HIV infection into the development of AIDS, since the order of magnitude of GM1 ganglioside expression on PBMs was AIDS greater than ARC greater than HIV+ asymptomatic = healthy controls. Our data indicate that PBMs from patients with AIDS are constitutively activated and suggest that activation directly correlates with disease progression.

Acquired Immunodeficiency Syndrome↗