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Biomedical subjects

C L King

Publications and source records attributed to C L King.

At least 55 records · Page 3Linked to original sources
PubMed1995

CD28 activation promotes Th2 subset differentiation by human CD4+ cells.

Ligation of CD28 provides a costimulatory signal to T cells necessary for their activation resulting in increased interleukin (IL)-2 production in vitro, but its role in IL-4 and other cytokine production and functional differentiation of T helper (Th) cells remains uncertain. We studied the pattern of cytokine production by highly purified human adult and neonatal CD4+ T cells activated with anti-CD3, phorbol 12-myristate 13-acetate (PMA) and ionomycin, or phytohemagglutinin (PHA) in the presence or absence of anti-CD28 in repetitive stimulation-rest cycles. Initial stimulation of CD4+ cells with anti-CD3 (or the mitogens PHA or PMA+ionomycin) and anti-CD28 monoclonal antibodies induced IL-4, IL-5 and interferon-gamma (IFN-gamma) production and augmented IL-2 production (6- to 11-fold) compared to cells stimulated with anti-CD3 or mitogen alone. The anti-CD28-induced cytokine production corresponded with augmented IL-4 and IL-5 mRNA levels suggesting increased gene expression and/or mRNA stabilization. Most striking, however, was the progressively enhanced IL-4 and IL-5 production and diminished IL-2 and IFN-gamma production with repetitive consecutive cycles of CD28 stimulation. The enhanced Th2-like response correlated with an increased frequency of IL-4-secreting cells; up to 70% of the cells produced IL-4 on the third round of stimulation compared to only 5% after the first stimulation as determined by ELISPOT. CD28 activation also promoted a Th2 response in naive neonatal CD4+ cells, indicating that Th cells are induced to express a Th2 response rather than preferential expansion of already established Th2-type cells. This CD28-mediated response was IL-4 independent, since enhanced IL-5 production with repetitive stimulation cycles was not affected in the presence of neutralizing anti-IL-4 antibodies. These results indicate that CD28 activation may play an important role in the differentiation of the Th2 subset in humans.

Animals↗
PubMed1995

Antigen presenting cell-independent cytokine and spontaneous in vitro IgE production in patients with atopic dermatitis: increased interferon-gamma production and lack of effects of in vivo low-dose interferon-gamma treatment.

Atopic dermatitis is characterized by elevated serum IgE concentrations and dysregulation of T-lymphocyte function. To examine the pattern of cytokine production associated with elevated IgE levels, phorbol ester plus ionomycin-stimulated production of interleukin (IL)-4, IL-5, and interferon-gamma (IFN-gamma) by blood mononuclear cells from 16 patients with atopic dermatitis was compared with that of 18 healthy subjects. Spontaneous in vitro IgE production was also studied longitudinally in patients receiving placebo or daily treatment with 0.05 mg/m2 IFN-gamma. Spontaneous in vitro IgE production and mitogen-driven IL-4 and IFN-gamma synthesis did not differ when patients were receiving interferon treatment compared with no treatment. Furthermore, ionomycin plus phorbol ester-stimulated mononuclear cells from patients with atopic dermatitis produced less IL-4 and more IFN-gamma than did cells from healthy subjects. IL-5 production by cells from patients with atopic dermatitis did not differ from that of cells from healthy subjects. The ratio of IL-4 to IFN-gamma produced in vitro was significantly lower (p = 0.04) in the cells of patients with atopic dermatitis (0.9) as compared with those of healthy subjects (2.7). The findings suggest that when circulating T cells are stimulated under antigen presenting cell-independent conditions, atopic dermatitis is not characterized by the shift in the reciprocal relationship between IL-4 and IFN-gamma production, which has been postulated to explain the pathogenesis of IgE elevation and the therapeutic action of IFN-gamma in patients with atopic dermatitis.

Adult↗
PubMed1995

Preferential recognition by human IgE and IgG4 of a species-specific Schistosoma haematobium serine protease inhibitor.

IgE induction in schistosomiasis is an important human response to infection, yet few specific parasite allergens have been characterized. One allergen of Schistosoma haematobium was found to be a species-specific surface antigen and a member of the serine protease inhibitor gene family (SH serpin). The purified recombinant SH serpin protein was used to characterize human isotypic responses to this antigen. Quantitative ELISA based on the recombinant antigen revealed marked IgG4 and IgE responses and a high degree of species specificity (IgG = 96%, IgG4 = 66%, and IgE = 95%) in sera from S. haematobium-infected persons. In contrast, ELISA based on soluble adult worm or egg antigens could not discriminate between species. There was no correlation between serpin-specific IgE and IgG4 levels in 41 infected persons. Further, serpin-induced antibody production in vitro indicated that IgE and IgG4 responses are not coordinately regulated.

Adolescent↗
PubMed1994

Comparison of four stainless steel heat exchangers for neonatal ECMO applications.

Conventional neonatal extracorporeal membrane oxygenation (ECMO) circuits utilize a heat exchanger distal to the oxygenator to replace ambient heat loss and maintain patient normothermia. A secondary function of the ECMO heat exchanger is to act as an arterial line bubble trap to protect the patient against accidental air embolism. Using an asanguinous recirculating test circuit, we measured and compared heat transfer properties, pressure drop, air trapping capabilities, and priming characteristics of four commercially available stainless steel heat exchangers currently being used in neonatal ECMO circuits: Avecor ECMOtherm, Gish HE-3, Gish HE-4, and Electromedics D1079. Manufacturers' product specifications were also compared. The pressure drop across all four heat exchangers was less than 10 mmHg with flow rates up to 500 ml/min. The Gish HE-3 and HE-4 were the easiest to prime and de-air, while the Electromedics D1079 was the most difficult. The heat exchangers with integral bubble traps (D1079 and HE-4) have superior air trapping capabilities. The ECMOtherm provided moderate air trapping capabilities ( greater than 7.3 ml +/- 1.5 ml) at flow rates under 300 ml/min. The low prime HE-3 was the poorest at trapping air; less than 1 ml at a 400 ml/min pump flow rate. Thermal analysis indicated that the D1079 had the highest performance factor, though all four heat exchangers had similar heat transfer rates and were capable of warming perfusate from 34 degrees to 37 degrees C on a single pass at pump flow rates of 500 ml/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Equipment Design↗
PubMed1993

IL-4- and IL-5-secreting lymphocyte populations are preferentially stimulated by parasite-derived antigens in human tissue invasive nematode infections.

Helminth infections in humans and animals are associated with strong T helper 2 (Th2) responses. To determine whether parasite-derived Ag preferentially expand a Th2-like cell population, a filter immunoplaque assay was used to enumerate the frequencies (F0) of PBMC and CD4(+)-enriched PBMC from individuals with helminth infections secreting selected cytokines in response to parasite-derived (PAg) and nonparasite antigens (NPAg). In 20 individuals with lymphatic filariasis, frequency analysis of PBMC secreting IL-4 and IFN-gamma indicated that the F0 of PAg-specific IL-4-secreting cells (geometric mean F0 (GM): 1/12,100) was 57-fold higher than the corresponding F0 of NPAg-reactive cells (GM: 1/692,000; p < 0.02). In marked contrast, the F0 of IFN-gamma-secreting cells responding to PAg (GM: 1/2,700) did not differ from those of cells specific for NAPg (GM: 1/3,400; p = 0.83). In another group of helminth-infected individuals, the F0 of highly enriched CD4+ cells secreting IL-4 and IL-5 in response to PAg (GMs: 1/2,600 and 1/5,600 CD4+ cells, respectively) were also found to be significantly higher than those specific for NPAg (GMs: 1/291,000 and 1/303,000 CD4+; p < 0.05 and p < 0.01, respectively), whereas the corresponding F0 of IFN-gamma- and granulocyte-macrophage-CSF-secreting cells were equivalent for PAg and NPag. Furthermore, the proportion of PAg-specific IL-4- and IL-5-secreting CD4+ cells relative to all cells secreting the given cytokine were approximately 29-fold higher than the proportion of NPAg-specific cells secreting these cytokines. Again, the corresponding proportions of Ag-specific IFN-gamma-and GM-CSF-secreting CD4+ cells were equivalent for PAg and NPAg. Thus, in this ex vivo system, a circulating population of IL-4- and IL-5-secreting (Th2-like) cells has been shown to exist in humans; PAg appears to expand these cells preferentially.

Adult↗
PubMed1993

IgE and IgG subclass regulation by IL-4 and IFN-gamma in human helminth infections. Assessment by B cell precursor frequencies.

Helminth infections, like atopic disorders, show characteristic elevations of serum IgE and IgG4. To examine the mechanisms underlying the regulation of these two isotypes and of the other IgG subclasses, the frequency (Fo) of isotype-specific B lymphocytes (Bc) from 11 patients with helminth infections was compared by filter-spot ELISA using fresh peripheral blood-derived lymphocytes after 14-day Ag stimulation in vitro. The role of IL-4 and IFN-gamma in the generation and regulation of Ag-driven isotype responses was determined. The Fo of freshly obtained lymphocytes (expressed/10(5) Bc) secreting polyclonal Ig for the following isotypes was: IgE (geometric mean = 0.72; range, 0 to 17.7); IgG4 (geometric mean = 4.9; range, 1.8 to 24.4); IgG1 (geometric mean = 134.3; range, 16.7 to 318). The Fo of IgE correlated with IgG4-secreting Bc among study subjects (r = 0.8, p < 0.01), however there was no association with the other isotypes. Parasite Ag added to cultured lymphocytes induced significant expansion in the number of Ig-secreting Bc for IgE and all IgG subclasses. In contrast, addition of a nonparasite Ag, tetanus toxoid, generated increased Fo of Ig-secreting Bc for IgG1, IgG2, and IgG3, and no expansion of IgG4 or IgE. The essential role of IL-4 in the expansion of IgE- and IgG4-secreting B cells in response to filarial Ag was demonstrated when simultaneous addition of neutralizing anti-IL-4 antibodies completely inhibited this response in all 11 patients studied. Neutralizing anti-IL-4 had no effect on either filarial or tetanus toxoid-driven expansion of IgG1-, IgG2-, or IgG3-secreting Bc. An inhibitory role of endogenously produced IFN-gamma was also shown when addition of neutralizing anti-IFN-gamma to cultures significantly augmented Ag-driven expansion of Bc-secreting IgE and all IgG subclasses; IgE, 0.4- to 9-fold; IgG4, 1.4- to 12-fold; IgG1, 1.6- to 13-fold; IgG2, 1.9- to 5-fold; and IgG3, 2.7- to 6-fold. This study demonstrates that parasite Ag stimulates Bc expansion in helminth-infected patients. Although this response for all five isotypes studied is down-regulated by IFN-gamma, the generation of only the IgE and IgG4 responses appears to be mediated selectively by IL-4. These findings support the concept that IgE and IgG4 production are linked and related to the quantities of IL-4 and IFN-gamma induced by Ag-specific T cells.

Antigens, Helminth↗
PubMed1993

IgE production in human helminth infection. Reciprocal interrelationship between IL-4 and IFN-gamma.

To determine whether there is a reciprocal relationship between IL-4 and IFN-gamma production in persons with parasite-induced elevations in serum IgE, PBMC were obtained from helminth-infected individuals with a broad range of serum IgE levels that fell into two distinct groups--extremely elevated (HI; n = 9; range, 4,129 to 18,400 ng/ml) or elevated (EL; n = 6; range, 403 to 1,018 ng/ml), relative to control subjects (NL; n = 7; range, 4 to 159 ng/ml). PBMC were stimulated in vitro, with Ag or mitogens, and IL-4 and IFN-gamma were measured by ELISA in culture supernatants. Helminth Ag- (but not tetanus toxoid) stimulated IL-4 production in eight of nine HI (range, 49 to 150 pg/ml) but was undetectable in either EL or NL (p < 0.01). In contrast, PBMC from EL produced significant levels of IFN-gamma to helminth Ag (GM = 358 pg/ml) compared with HI (GM = 89 pg/ml; p = 0.02) and NL (GM = 9 pg/ml; p < 0.001). Tetanus toxoid induced comparable levels of IFN-gamma among the three groups. Mitogen-driven IL-4 production was ninefold greater in HI [geometric mean (GM) = 913 pg/ml] versus EL (GM = 111 pg/ml; p < 0.01) and NL (GM = 193 pg/ml; p < 0.001) and correlated with serum IgE levels (r = 0.8; p < 0.01). Mitogen-driven IFN-gamma synthesis was equivalent among the groups. Although parasite Ag-driven IL-4 secreting CD4+ cells were detected (by ELISPOT) among infected subjects with both high and low serum IgE levels, the number of IL-4 exceeded that of IFN-gamma-secreting cells among individuals with elevated serum IgE levels, whereas the opposite relationship existed among subjects with normal serum IgE. In a subpopulation of infected individuals (n = 4), parasite-Ag added to PBMC cultures induced polyclonal IgE that was directly associated with the parasite-Ag-driven IL-4 production and inversely related to IFN-gamma synthesis in PBMC supernatants from parallel cultures. Furthermore, neutralizing anti-IFN-gamma antibody augmented both parasite-driven IL-4 synthesis and IgE production in vitro (n = 4). The data indicate that helminth-induced serum IgE levels are directly related to an increased capacity by PBMC to produce IL-4 and inversely associated to IFN-gamma production. It further supports the concept that IL-4 and IFN-gamma reciprocally regulate IgE in vivo.

Acute Disease↗
PubMed1993

Cytokine control of parasite-specific anergy in human lymphatic filariasis. Preferential induction of a regulatory T helper type 2 lymphocyte subset.

The immunological mechanisms involved in maintenance of an asymptomatic microfilaremic state (MF) in patients with lymphatic filariasis remain undefined. MF patients have impaired filarial antigen (Ag)-specific lymphocyte proliferation and decreased frequencies (Fo) of Ag-specific T cells, and yet elevated serum IgE and antifilarial IgG4. To investigate the mechanism of Ag-specific anergy in MF patients in contrast to amicrofilaremic individuals with chronic lymphatic obstruction (CP), the Fo of Ag-specific lymphocytes from peripheral blood mononuclear cells secreting either IL-4 or IFN-gamma were assessed by filter spot enzyme-linked immunosorbent assay, and IL-10 and transforming growth factor-beta (TGF-beta) mRNA transcript levels were assessed by a semiquantitative reverse transcriptase polymerase chain reaction technique. The Fo of filaria-specific IL-4-secreting lymphocytes were equivalent in both MF (geometric mean [GM] = 1:11,700) and CP (GM = 1:29,300 P = 0.08), whereas the Fo of IFN-gamma-secreting lymphocytes were lower in MF (GM = 1:39,300) than in CP (GM = 1:4,200, P < 0.01). When the ratio of IL-4/IFN-gamma (T helper type 2 [Th2]/Th1)-secreting cells was examined, MF subjects showed a predominant Th2 response (8:1) compared with a Th1 response in CP individuals (1:4). mRNA transcript levels of IL-10 were also significantly elevated in MF compared with CP individuals (P < 0.01). Further, IL-10 and TGF-beta were shown to have a role in modulating the Ag-specific anergy among MF subjects, in that neutralizing anti-IL-10 or anti-TGF-beta significantly enhanced lymphocyte proliferation response (by 220-1,300%) to filarial Ags in MF individuals. These findings demonstrate that MF subjects respond to parasite antigen by producing a set of suppressive cytokines that may facilitate persistence of the parasite within humans while producing little clinical disease.

Adult↗
PubMed1993

Cytokines and immediate hypersensitivity in protective immunity to helminth infections.

Infection with tissue-invasive helminth infections characteristically induces immunological responses associated with immediate hypersensitivity such as IgE elevations, tissue and peripheral blood eosinophilia, and mast cell hyperplasia. Specific sets of cytokines appear to regulate these responses; the resulting responses reflect the balance of upregulatory and inhibitory signals these cytokines provide. The nature of these cytokines and their role in both protective immunity and pathogenesis in helminth infections of humans is the subject of this review.

Animals↗
PubMed1992

Parallel regulation of IL-4 and IL-5 in human helminth infections.

To investigate the relationship between cytokine production and the increased levels of serum IgE and peripheral eosinophilia commonly accompanying human helminth infections, we studied the ability of PBMC of normal (N1) (n = 18) and eosinophilic individuals with helminth infections (H1) (n = 9) to produce IL-3, IL-4, IL-5, granulocyte-macrophage-CSF, and IFN-gamma in vitro after stimulation with PMA (50 ng/ml) and ionomycin (1 microgram/ml). The two groups differed in both the levels of serum IgE and eosinophilia. For mitogen-induced production of granulocyte-macrophage-CSF and IFN-gamma, there was no difference in cytokine production between the two groups. In marked contrast, supernatants from PBMC of infected individuals had significantly higher levels of IL-4 (mean = 213 pg/ml for N1 and 944 pg/ml for H1, p less than 0.02), IL-5 (mean = 180 pg/ml for N1 and 1118 pg/ml for HL, p less than 0.001), and IL-3 (mean = 13900 pg/ml for N1, 28029 pg/ml for H1, p less than 0.05). In addition, helminth-infected patients had approximately 5-fold greater numbers of T cells capable of producing IL-5 and 2.5-fold greater frequency of IL-4-secreting cells than did normal individuals; GM-CSF- and IFN-gamma-producing T cell numbers were not significantly different in the two groups. IL-3-producing cell frequencies could not be evaluated by this method. There was a direct correlation between IL-4 production and IL-5 production at the level of both protein production and frequency of T cells capable of producing these cytokines. These data indicate that individuals with reactive eosinophilia and elevated serum IgE have an expanded population of lymphocytes producing IL-4 and IL-5 and the association of the two suggests that the regulation of IL-4 and IL-5 may be linked.

CD4-Positive T-Lymphocytes↗
PubMed1992

Schistosoma mansoni: silver ion (Ag +) stimulates and reversibly inhibits lipid-induced cercarial penetration.

Certain long-chain polyunsaturated fatty acids (FA) found on mammalian skin trigger cercariae to penetrate and transform into schistosomules; however, the mechanism by which FAs stimulate cercariae is unknown. In order to determine whether argentophilic papillae concentrated at the apical region of the cercariae are the chemoreceptors that may mediate cercarial response to FAs, an assay assessed the proportion of cercariae that penetrated a 0.25% agar matrix in the presence (61%) and the absence (2.3%) of linolenic acid at 0.22 mM. Silver nitrate (Ag+) which selectively binds to cercarial papillae (Short and Cartrett, J. Parasitol. 59, 1041, 1973) is nontoxic (at 0.09 mM used in this study) as demonstrated by the ability of Ag+ treated cercariae to mature successfully into adult worms (8.8% maturation compared to 10.2% of untreated controls, n = 5) after subcutaneous injection. When Ag+ was added to cercarial suspensions, penetration into linolenic-impregnated agar was significantly inhibited (80.8%). Washing cercariae free of Ag+ reversed this inhibition. These data, as well as observations that both argentophilic papillae and cercarial response to FAs disappeared within 3 to 4 hr after mechanical conversion to schistosomules, implicate argentophilic papillae on cercariae as chemoreceptors for lipid stimulation.

Agar↗
PubMed1992

Immunologic tolerance in lymphatic filariasis. Diminished parasite-specific T and B lymphocyte precursor frequency in the microfilaremic state.

To explore the mechanisms of antigen-specific immune unresponsiveness seen in microfilaremic patients with bancroftian filariasis, T and B cell precursor frequency analysis was performed using PBMC from individuals with either asymptomatic microfilaremia (MF, n = 7) or chronic lymphatic obstruction (CP, n = 20). Highly purified CD3+ cells were partially reconstituted with adherent cells and their proliferative response to parasite antigens determined in cultures of T cells by limiting dilution analysis. A filter immunoplaque assay also assessed the frequency of both total and parasite-specific Ig-producing B cells. While the lymphocyte proliferation to mitogens and to a nonparasite antigen (Streptolysin-O, [SLO]) were similar in all groups of patients, the frequency of parasite-specific CD3+ T cells was significantly lower (geometric mean [GM], 1/3,757) in MF patients when compared to that in CP patients (GM 1/1,513; P less than 0.001). Similarly, the proportion of lymphocytes producing parasite-specific IgE or IgG was significantly lower in MF patients (IgE mean, 0.2%; IgG mean, 0.33%) compared with CP patients (IgE mean, 3.2%; IgG mean, 1.76%; P less than 0.05 for both comparisons). These observations imply that low numbers of parasite-specific T and B lymphocytes may be partially responsible for the severely diminished capacity of lymphocytes from patients with MF to produce parasite-specific antibody and to proliferate to parasite antigen in vitro. Such differences in parasite-specific lymphocyte responses suggest that tolerance by clonal anergy may be a critical mechanism for maintaining the microfilaremic state.

Animals↗
PubMed1991

Frequency analysis of IgE-secreting B lymphocytes in persons with normal or elevated serum IgE levels.

The immunoregulatory mechanisms that determine the high serum IgE antibody levels in disorders such as helminth parasite infections and the hyper-IgE recurrent infection syndrome (HIE) remain poorly understood. To assess whether elevated serum IgE levels result from an increased number of B lymphocytes committed to IgE production, the proportion of IgE-producing B lymphocytes was determined by a filter immunoplaque assay using PBMC from persons with a broad range of serum IgE levels that included normal persons (n = 9) and patients with loiasis (n = 12), tropical pulmonary eosinophilia (TPE) (n = 6), lymphatic filariasis (n = 28), and HIE (n = 8). PBMC from these persons were assessed for production of in vitro IgE. The geometric mean number of IgE-secreting cells in 10(5) B lymphocytes in PBMC was 0.42 (range 0-2.2) in normal persons, 5.6 (range 0.1-35.5) among patients with loiasis, 9.4 (range 0-53.2) among patients with lymphatic filariasis, 52 (range 31.5-115) among patients with TPE, and 218 (range 56-1404) among patients with HIE. When all study subjects were grouped, there were significant correlations with serum IgE levels (r2 = 0.78; p less than 0.0001) and net spontaneous in vitro IgE production (r2 = 0.8; p less than 0.0001). Estimates of the amount of IgE production per B lymphocyte were similar among normal persons, patients with filarial infections, and patients with TPE (geometric means of 134, 96, and 141 pg/ml/cell, respectively); in contrast, for HIE patients, IgE production by individual B cells was significantly lower (geometric mean 28 pg/ml/cell; p less than 0.001). These observations demonstrate that clonal expansion of IgE-producing B lymphocytes is a major mechanism underlying the elevated serum IgE levels seen in persons with hyper-IgE states.

Adolescent↗
PubMed1991

Regulation of the immune response in lymphatic filariasis and onchocerciasis.

The persistence of microfilariae in the blood or skin accompanied by a prominent eosinophilia and elevated serum IgE levels are common features of human infection with filarial parasites. In this review Christopher King and Thomas Nutman discuss recent findings on the role of interleukin 4 (IL-4), IL-5 and gamma-interferon (IFN-gamma) in the induction of these immediate hypersensitivity responses. They discuss the role of hypersensitivity in immunity, the development of immune tolerance to filarial antigens and suggest that could explain the impaired immune response of some individuals to filarial infections and the persistence of the microfilaremic state.

Animals↗
PubMed1990

Enumeration of IgE secreting B cells. A filter spot-ELISA.

To assess the frequency of IgE producing cells in humans a filter immunoplaque assay has been developed to detect IgE secretion from individual B lymphocytes in unfractionated peripheral blood mononuclear cells (PBMC). PBMC were incubated in microfilter plates containing nitrocellulose membranes coated with polyclonal anti-human IgE antibody, and the IgE production by a single cell was detected using a specific anti-human IgE monoclonal antibody followed by enzymatic development. The products of the enzymatic reaction were visualized as blue plaques on the membranes. The assay was both sensitive and specific as determined by: (1) a near 1:1 correlation between direct cell counts of an IgE producing myeloma cell line (U266) and the number of plaques in the filter immunoassay; and (2) the absence of detectable plaques generated by human B cells transformed by Epstein-Barr Virus (EBV) and producing only IgG or IgM. The presence of other cell types in PBMC did not affect the ability to detect IgE secreting cells. Replicate cultures of highly purified B lymphocytes, first transformed with EBV and then stimulated with recombinant human interleukin-4, produced IgE levels in culture supernatants that correlated closely with the number of IgE producing cells (r = 0.93; P less than 0.001). Furthermore, using the same transformed cells, the number of IgE secreting cells assessed by the immunoplaque assay was significantly correlated (r = 0.94; P = 0.002) with the number of IgE producing cells assessed by immunofluorescence staining of intracytoplasmic IgE. This assay provides a simple and direct method to assess the frequency of IgE producing lymphocytes in humans.

B-Lymphocytes↗
PubMed1990

Cytokine regulation of antigen-driven immunoglobulin production in filarial parasite infections in humans.

To define the immunoregulatory mechanisms underlying serum IgE levels found in patients with filariasis, we studied polyclonal IgE production by peripheral blood mononuclear cells (PBMC) from 15 patients with filarial infections, with a focus on the role of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) in the generation and regulation of the response. Spontaneous in vitro IgE production was elevated in 10 of the 15 patients (836-6,464 pg/ml; normals, less than 500 pg/ml). Addition of filarial parasite antigen to PBMC cultures significantly stimulated polyclonal IgE production in an antigen dose-dependent manner in 10 of 12 patients tested (P less than 0.001). The essential role of IL-4 in the generation of this response was demonstrated when simultaneous addition of anti-IL-4 completely inhibited antigen-stimulated IgE production in all 10 patients studied. An inhibitory role of endogenously produced IFN-gamma was also indicated when the addition of anti-IFN-gamma to the cultures significantly augmented filarial antigen-stimulated IgE production by 33-1,238% in these same patients. Addition of 10-1,000 U/ml of recombinant human IFN-gamma to PBMC completely inhibited parasite antigen-induced IgE production. This study demonstrates that filarial antigen-stimulated IgE production in patients with filariasis is mediated by IL-4 and down regulated by IFN-gamma and suggests that the amount of IgE produced depends on the relative quantity of IL-4 and IFN-gamma generated by parasite-specific T cells.

Antibody Formation↗