Detection of serum antibody by the antimitogen assay against streptococcal erythrogenic toxins. Age distribution in children and the relation to Kawasaki disease

We describe a new method to measure human serum antibody against streptococcal erythrogenic toxins that uses inhibition of lymphocyte mitogenicity of the toxins as the indicator. Sera from 53% of 53 Kawasaki disease patients contained specific inhibitory activity against A toxin, whereas only 15% had serum inhibitory activity against B toxin. The specific anti-A toxin serum inhibitor was found in 10% of 118 age-matched control patients suffering from various infections and allergic diseases (p = 0.001, compared to Kawasaki disease patients). Serum inhibitory activity was detected in a small number of patients with beta-hemolytic streptococcal infection (3/19) and in none of the age-matched healthy children (0/17). However, four of seven cord blood sera samples and five of 13 sera samples from healthy neonates contained the inhibitor, a result suggesting passive transfer from mothers. Most of the antimitogen-positive sera were also positive by ELISA of IgG antibody against A toxin, and IgG fractions of the positive sera remained positive in both assays. Thus, it is possible that the specific serum inhibitor detected by the antimitogen assay represents anti-A toxin antibody. The role of toxin-producing bacteria in the pathogenesis of Kawasaki disease remains to be investigated.     

Altered antibody isotype in cystic fibrosis: possible role in opsonic deficiency

Patients with cystic fibrosis (CF) whose respiratory tracts are colonized with Pseudomonas aeruginosa (PA) may develop a specific opsonic deficiency for alveolar macrophage phagocytosis of PA. We examined the possible role of altered antibody (Ab) isotype in this phenomenon by measuring serum levels and distribution of IgG and IgG subclass Ab (IgG1, IgG2, IgG3, and IgG4) to the major opsonic immunodeterminant, serotype-specific lipopolysaccharide (LPS), by means of enzyme-linked immunosorbent assays employing monoclonal secondary antibodies, and comparing these results to the serum opsonic capacity in an in vitro murine alveolar macrophage phagocytic assay. Twenty-one patients with CF who were colonized with PA had approximately a 30-fold elevation of PA LPS IgG Ab levels and higher IgG subclass 1-4 Ab compared to 10 uncolonized patients with CF and 11 healthy controls (p less than 0.05-0.0005 depending on the isotype). Colonized patients with CF had a shift in PA LPS Ab distribution toward IgG3 compared to uncolonized patients with CF (p less than 0.02). A surprising finding was that uncolonized patients with CF had lower levels (p less than 0.05) and proportion (p less than 0.002) of PA LPS IgG2 Ab than controls, with an apparent shift to higher levels and proportion of PA LPS IgG4 (p less than 0.01). Serum from colonized patients with CF showed diminished opsonic capacity for phagocytosis of PA compared to uncolonized patients and controls (p less than 0.005), with 42% showing inhibitory activity. Functional Ab was also found to be inhibitory at high (greater than 500 ng/ml) concentrations. Serum opsonic capacity appeared to include a noncomplement cofactor for optimal activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Defective regulation of the protective IgE response against intestinal helminth Ascaris lumbricoides in malnourished children

It is well established that malnutrition affects the immune response and increases the susceptibility to parasitic infection. In the present study we evaluated some aspects of the cellular and cytokine network that regulate the IgE responses, which are important components of host defence mechanisms against helminthic parasites in children infected with the intestinal helminth Ascaris lumbricoides, and with differing degrees of malnutrition. We found a defective T cell response in malnourished children, as indicated by diminished levels of circulating total (CD3+), helper (CD4+), IL-2-receptor-bearing (CD4+CD25+) and memory helper T cell responses (CD4+CD45RO+) in keeping with the decreased specific IgE levels against Ascaris lumbricoides. In contrast, the proportions of total B cells (CD20+), and those bearing the low-affinity IgE receptor (CD23+) were increased in the moderated malnourished children. Moreover, serum IL-4 levels and total IgE were also increased in these children. We suggest that malnutrition can cause an imbalance in T cell subpopulations that may lead to a defective T cell maturation and a decreased specific anti-Ascaris IgE response thus increasing the susceptibility to such infections. The high levels of total IgE observed may be related to a non-specific stimulation of the proliferation of activated B cells, probably caused by helminthic parasites and other infectious agents that are frequent in malnourished children.     

Acute osteomyelitis and septic arthritis in children

OBJECTIVE: To review the clinical presentation, clinical management and organisms responsible for acute haematogenous osteomyelitis (AHO) and septic arthritis (SA) in the post Haemophilus influenzae type B (Hib) vaccine era and to evaluate current Australian antibiotic guidelines for these conditions. METHODS: A retrospective chart review of children less than 16 years of age presenting to The Children's Hospital at Westmead in the period from January 1998 to July 2002 with an ICD discharge code consistent with AHO or SA. RESULTS: During the 4 1/2-year period 120,511 children were admitted to The Children's Hospital at Westmead. There were 102 cases of AHO and 47 cases of SA during this time. An organism was identified either by blood culture or tissue biopsy in 45% of children with AHO and 38% with SA. Staphylococcus aureus was the most common identifiable causative organism accounting for 76% of isolated organisms in AHO and 39% of isolated organisms in SA. Methicillin-resistant S. aureus (MRSA) was responsible for 9% of AHO and 6% of SA cases. There were no cases due to Haemophilus influenzae or Kingella kingae during the study period. The majority (66%) of children with AHO were managed non-operatively with intravenous and then oral antibiotics. Thirty-five (34%) children had operative treatment to drain pus. In contrast, 74% of the patients with SA had one or more surgical procedures performed to drain pus from involved joints. CONCLUSIONS: Staphylococcus aureus remains the most common organism causing AO and SA; however, community-acquired methicillin-resistant strains are now occurring. Haemophilus influenzae is no longer a common cause of SA. Our study supports the current Australian antibiotic guidelines that recommend flucloxacillin alone as the empiric treatment of choice of both AHO and SA in children fully immunised against Hib. However the possibility of community-acquired MRSA should be considered, particularly in high risk groups such as indigenous Australian children or children from regional areas with a high rate of community-acquired MRSA.     

Development of B Lymphocyte Function in Childhood

ABSTRACT. The capacity of blood lymphocytes of children aged from birth to six years to produce immunoglobulins was studied in vitro at the cell level using a direct B lymphocyte activator (Epstein-Barr virus) or a T lymphocyte dependent B lymphocyte activator (pokeweed mitogen). Umbilical cord blood lymphocytes secreted IgM at adult levels after Epstein-Barr virus stimulation, while the ability to synthesize IgG and IgA increased up to the ages of 1 and 2 years, respectively, but not beyond this period. IgG3 production preceded that of the other IgG subclasses. The T lymphocyte dependent IgM synthesis was low at birth, but approached adult levels at two years of age. T cell dependent IgG and IgA secretion, however, remained reduced even up to 6 years of age.     

Development of B lymphocyte function in childhood

The capacity of blood lymphocytes of children aged from birth to six years to produce immunoglobulins was studied in vitro at the cell level using a direct B lymphocyte activator (Epstein-Barr virus) or a T lymphocyte dependent B lymphocyte activator (pokeweed mitogen). Umbilical cord blood lymphocytes secreted IgM at adult levels after Epstein-Barr virus stimulation, while the ability to synthesize IgG and IgA increased up to the ages of 1 and 2 years, respectively, but not beyond this period. IgG3 production preceded that of the other IgG subclasses. The T lymphocyte dependent IgM synthesis was low at birth, but approached adult levels at two years of age. T cell dependent IgG and IgA secretion, however, remained reduced even up to 6 years of age.     

Production of antibodies to staphylococcal superantigens in atopic dermatitis

Staphylococcal superantigens (SAG) are implicated in the inflammation of atopic dermatitis. As SAG mediated diseases may be modified by specific antibodies, the antibody response to SAG in atopic dermatitis was investigated. Immunoglobulin (Ig) G to staphylococcal enterotoxin A (SEA), staphylococcal enterotoxin B (SEB), and toxic shock syndrome toxin 1 (TSST-1) were measured by sandwich enzyme linked immunosorbent assay (ELISA) in 74 children with atopic dermatitis and 111 controls. Controls had detectable IgG to SEA, SEB, and TSST-1, which increased with age. Atopic dermatitis subjects had an increased response to SEB at 6 months to 2 years (76% v 42%) and 2 to 7 years (79% v 57%), and equivalent responses to SEA and TSST-1, compared to controls. It is suggested that increased responses to SEB relate to increased colonisation and hence exposure to superantigen producing staphylococcus in atopic dermatitis, and that inflammation of atopic dermatitis is not caused by an inability to make antibody to SAG.     

Production of antibodies to staphylococcal superantigens in atopic dermatitis.

Staphylococcal superantigens (SAG) are implicated in the inflammation of atopic dermatitis. As SAG mediated diseases may be modified by specific antibodies, the antibody response to SAG in atopic dermatitis was investigated. Immunoglobulin (Ig) G to staphylococcal enterotoxin A (SEA), staphylococcal enterotoxin B (SEB), and toxic shock syndrome toxin 1 (TSST-1) were measured by sandwich enzyme linked immunosorbent assay (ELISA) in 74 children with atopic dermatitis and 111 controls. Controls had detectable IgG to SEA, SEB, and TSST-1, which increased with age. Atopic dermatitis subjects had an increased response to SEB at 6 months to 2 years (76% v 42%) and 2 to 7 years (79% v 57%), and equivalent responses to SEA and TSST-1, compared to controls. It is suggested that increased responses to SEB relate to increased colonisation and hence exposure to superantigen producing staphylococcus in atopic dermatitis, and that inflammation of atopic dermatitis is not caused by an inability to make antibody to SAG.     

IgG subclass deficiency in children with congenital heart disease

This study of 66 children with congenital heart disease found 26 (39%) with IgG subclass deficiency, the majority being of the IgG₄ isotype. Conventional immunoiogical assessment (IgG, IgA, IgM, T cell) revealed 21 (32%) with immunodeficiency, while inclusion of IgG subclass assessment revealed a total of 35 (53%) of the 66 children had immuno-deficiency. Children with conotruncal lesions appeared to be predisposed to immunodeficiency affecting T cells and IgG subclasses (especially IgG₄) while those with shunt and stenotic lesions had a broad spectrum of immunoglobulin deficiencies. There was significant correlation between immunodeficiency and proneness to infection in these children (p < 0.01). These results suggest that immunodeficiency is a frequent occurrence in children with congenital heart disease, and that IgG subclass measurements should be added to the diagnostic work-up.     

Abnormal signal transduction in a patient with severe combined immunodeficiency disease

We have studied an 8-yr-old male patient with adenosine deaminase-positive severe combined immunodeficiency disease with a normal number of peripheral CD3+, T cell receptor-alpha beta+ T cells. The majority of these T cells expressed the CD8 molecule and were oligoclonal in nature as proven by Southern blot analysis of the T cell receptor genes. T cells failed to proliferate in vitro either upon stimulation with T cell mitogens or when stimulated with a combination of the phorbol ester phorbol myristate acetate and the Ca-ionophore ionomycin. High doses of recombinant IL-2, when added to in vitro cultures, were able to restore proliferation induced by phorbol myristate acetate and ionomycin but the response to concanavalin A remained severely defective. However, activation of the patient's T cells with phytohemagglutinin or concanavalin A induced an increase of free cytoplasmic Ca++, which was 2- to 5-fold higher than in normal CD8+ T cells. Furthermore, phorbol myristate acetate or phytohemagglutinin induced the translocation of protein kinase C from cytosol to plasma membrane. Analysis of membrane phospholipid composition of the patient's T cells disclosed that the ratio of phosphatidylcholine to phosphatidylserine was 5-fold higher than in normal T cells. The abnormal Ca++ response after activation with T cell mitogens as well as the high phosphatidylcholine/phosphatidylserine ratio may be causally linked to the defective in vitro T cell proliferation. Because the capacity of T lymphocytes to produce or respond to IL-2 may vary, the oligoclonality of the T cells of the patient should be considered as well in the explanation of defective cell proliferation.     

Effect of breast milk of healthy and allergic mothers on in vitro stimulation of cord blood lymphocytes

Maternal milk has beneficial effects on the development and function of the newborn's immune system. Whether the milk of allergic mother has the same effects as the milk of healthy mothers is not yet quite clear. To contribute to the characterization of its immunomodulatory action, we tested the effect of milk of healthy and allergic mothers on the proliferation and immunoglobulin formation in cultures of cord blood mononuclear leucocytes (CBML) of newborns of healthy and allergic mothers. CBML proliferation was tested by (3)H-thymidine incorporation, IgM, IgG and IgA production by reverse ELISPOT. CBML response was examined in unstimulated cultures and after stimulation with polyclonal activators in the presence or absence of colostrum or milk. The cells of children of allergic mothers have a significantly higher proliferative activity than those of children of healthy mothers. Maternal colostrum/milk in high doses markedly suppresses cell proliferation after stimulation with polyclonal activators, whereas lower milk doses in the cultures have no such effect and exert a rather stimulatory action. Immunoglobulin production by cord blood lymphocytes is also different in the two groups of children. Low basal immunoglobulin formation is increased after stimulation with a strong polyclonal activator of B cells--Bacillus firmus, CBML of children of allergic mothers produce more IgA than those of children of healthy mothers. The stimulated production of all immunoglobulin classes in cells of children of healthy mothers is still enhanced by colostrum/milk. Children of allergic mothers show a markedly increased production of only IgM and IgA. The effect of healthy and allergic colostrum and milk on cell proliferation and immunoglobulin production is similar. The lymphocytes of children of allergic mothers differ from the lymphocytes of children of healthy mothers in their proliferative activity and the ability to form immunoglobulin already at birth.     

Anaphylaxis to L-asparaginase during treatment for acute lymphoblastic leukemia in children--evidence of a complement-mediated mechanism

L-Asparaginase (l-Asp) is widely used as an effective drug against childhood and adult acute lymphoblastic leukemia (ALL). However, it is immunogenic in humans and may lead to hypersensitivity reactions. The immunological basis of these reactions is not clear. Since the presence of l-Asp specific IgG-antibodies seems to correlate better with clinical reactions than IgE-antibodies and IgG-antibodies are known to be able to fix and activate the complement system, we speculated that the mechanism of anaphylaxis may be complement- rather than IgE-mediated. We analyzed 24 children with ALL (age 2-15 yr) for changes in the complement system during l-Asp infusions. Chemotherapy was administered according to the CoALL 82 protocol which is derived from the CoALL 80 protocol recently published. The formation of specific antibodies of IgM and IgG classes against l-Asp was monitored by a solid phase ELISA. The immunological responsiveness of individual patients varied over a wide range but both types of antibodies were induced. Anaphylactic reactions were observed on eight occasions in eight children. The infusions in the remaining 16 patients were tolerated without clinical reactions. Significant activation of complement was demonstrated in seven of eight reaction occasions and in none of the occasions without reactions. The most important complement activation parameter monitored was the C3 split product C3d measured in EDTA-plasma. We conclude that anaphylaxis to l-Asp in patients with ALL can be explained in most instances on the basis of complement activation induced by the formation of immune complexes of l-Asp and specific antibodies of IgM and IgG classes.     

Development of autoantibodies to islet antigens during childhood: implications for preclinical type 1 diabetes screening

Abstract: Objective:  Serum islet antibodies signify increased risk for type 1 diabetes (T1D). Knowledge of the relationship between age and seroconversion would guide screening for at-risk individuals. We aimed to determine the effectiveness of islet antibody screening in early childhood, in particular the proportion of negative children who subsequently seroconverted.
Methods:  We identified 554 children with a first-degree relative with T1D who had tested negative for islet cell antibodies (ICA) and insulin autoantibodies (IAA) when first screened at a mean age of 7.2 yr. Of 423 who were eligible, 350 consented to re-testing for ICA and IAA and antibodies to glutamic acid decarboxylase (GADAb) and tyrosine phosphatase-like insulinoma antigen IA-2 (IA2Ab) at a mean age of 11.1 yr. GADAb and IA2Ab were measured in 239 of the initial stored samples.
Results:  Of the 350 children who tested negative at first screening, 12 (3.4%) subsequently seroconverted, becoming positive for ICA (n = 4), IAA (n = 7), GADAb (n = 6) or IA2Ab (n = 2). Of 239 initially negative for ICA and IAA, 8/239 (3.3%) now tested positive for GADAb (n = 7) or IA2Ab (n = 1). Four of these children were positive for GADAb in both tests; the one child initially positive for IA2Ab only was positive for all four antibodies 4.6 yr later and developed diabetes.
Conclusion:  Screening for ICA and IAA failed to identify 2–3% of genetically at-risk children who subsequently developed islet antibodies. Testing for GADAb and IA2Ab would not have avoided this. Maximizing the sensitivity of detecting risk for T1D requires repeat screening for islet antibodies throughout childhood.     

Relation of streptococcal pyrogenic exotoxin C as a causative superantigen for Kawasaki disease

We previously reported that the frequency of TCRBV2 and TCRBV6S5-bearing T-cells was high in patients in the acute phase of Kawasaki disease (KD) and that streptococcal pyrogenic exotoxin C (SPE-C) was a potent stimulator of these TCRBV-bearing T-cells. To further elucidate the pathogenesis of KD, we examined the T-cell receptor (TCR) repertoire, human leukocyte antigen (HLA)-DRB1 genotype, and antibody responses to recombinant(r) SPE-C in patients with KD. We also performed in vitro stimulation with rSPE-A and rSPE-C of peripheral blood mononuclear cells from healthy donors and characterized the reacting T-cells. The percentage of T-cells bearing TCRBV2 and TCRBV6S5 was high in patients in the acute stage of KD. rSPE-C stimulation of PBMC from healthy donors induced expansion of TCRBV2 and TCRBV6S5-bearing T-cells. Furthermore, serum levels of anti-SPEC antibodies, which did not display antimitogenic activity, were higher in patients with acute KD than in age-matched controls. The frequencies of the DRB1*04051, 0406, and 0901 were high, whereas that of the DRB1*1101 was low among patients with KD as compared with the healthy adults.     

Peripheral blood lymphocyte subsets in children with frequent upper respiratory tract infections

It is a common and well-known fact that infants and preschool children undergo frequent episodes of upper respiratory tract infections. The majority of these children do not have a recognized immunodeficiency. The aim of the present study was to evaluate the effects of frequent upper respiratory tract infections on cellular immunity, using peripheral blood lymphocyte subsets and activation markers as defining parameters. The study group consisted of 16 children (aged 2-6 years) with frequent upper respiratory tract infections; 30 age-matched healthy children served as controls. Peripheral blood T, B, NK cells; T lymphocyte subsets; naive and memory cells; and activation markers were analyzed by using monoclonal antibodies and flow cytometry. White blood cell count (WBC) was found to be markedly increased in the study group compared to controls (p < 0.05). The absolute number of lymphocytes was also higher than that of the healthy children. The relative size of the CD3+CD8+ T lymphocytes and the relative and absolute numbers of CD3-CD16+56+ NK cells were found to be higher in patients than the controls. All the remaining percentages and numbers of the T cell subgroups including naive and memory cells and B lymphocytes did not show any difference, while CD3+CD25+ cell numbers were markedly increased (p < 0.05). In conclusion, the examination of peripheral blood lymphocyte subsets in children with frequent upper respiratory tract infections is important in evaluating cellular immune alterations due to antigenic stimulation; however, it is neither essential nor cost-effective in the management of the disease. This study has shown that both the percentage and absolute numbers of peripheral blood lymphocyte subsets maintain their normal status in children with frequent upper respiratory tract infections.     

神经母细胞瘤脂类提取物对NKT细胞激活作用的实验研究

目的 研究神经母细胞瘤脂类提取物对健康儿童自然杀伤T（NKT）细胞增殖程度和对NKT细胞介导的对自身肿瘤细胞的细胞毒作用的影响。方法 甲醇／氯仿法提取神经母细胞瘤脂类提取物作为刺激物，采集健康儿童外周血单核细胞，培养出成熟的树突细胞，采集并分离同一个体外周血T细胞与树突细胞共同培养，分别加入脂类提取物或（和）白细胞介素15（IL－15）和粒－单系细胞集落刺激因子（GM－CSF）。测定各组T细胞的增殖程度的变化，流式细胞仪测定NKT细胞占T细胞的比例（NKT／T）并分选出NKT细胞对神经母细胞瘤细胞毒作用。结果 肿瘤脂类提取物刺激组T细胞增殖程度、NKT／T比例、NKT细胞毒作用高于对照组（P＝0．043；P＝0．020；P＝0．032）。共刺激组（肿瘤脂类提取物＋IL－15＋GM－CSF）T细胞增殖程度、NKT／T比例、NKT细胞毒作用高于对照组（P＝0．001；P＝0．001；P＝0．020），肿瘤脂类提取物刺激组（P＝0．004；P＝0．030；P＝0．010）和细胞因子刺激组（P＝0．044；P＝0．049；P＝0．048）。结论 神经母细胞瘤脂类提取物可以有效激活NKT细胞，发挥对自身肿瘤细胞的细胞毒作用。细胞因子IL－15和GM－CSF可以增强脂类提取物的激活作用。     

Activation of NKT Cells by IL 15 Plus GM CSF Stimulation and Its Cytotoxicity to Neuroblastoma Cells

Ｎｅｕｒｏｂｌａｓｔｏｍａ (ＮＢ)ｉｓｔｈｅｍｏｓｔｃｏｍｍｏｎｍａｌｉｇ ｎａｎｔｔｕｍｏｒｏｆｔｈｅｓｙｍｐａｔｈｅｔｉｃｎｅｒｖｏｕｓｓｙｓｔｅｍｉｎｃｈｉｌ ｄｒｅｎ .Ｔｈｅｌｏｎｇ ｔｅｒｍｓｕｒｖｉｖａｌｉｓｌｏｗｗｉｔｈｆｒｅｑｕｅｎｔｒｅ ｃｕ     

Increased production of serum IgA-class antibody to lipid A in Kawasaki disease

BACKGROUND: The etiology of Kawasaki disease (KD) remains unknown. To investigate whether a conventional bacterial antigen is involved in the pathogenesis of KD, we studied the serum response to lipopolysaccharide (LPS). METHODS: We measured the serum levels of IgG-, IgM- and IgA-class antibodies (Ab) to lipid A, a toxic site of LPS, using enzyme-linked immunosorbent assay in 20 patients with KD, 11 patients with Gram-negative bacterial infection (GNBI), 27 healthy children and 12 healthy adults. RESULTS: The serum levels of anti-lipid A IgG, IgM and IgA tended to increase with advancing age in healthy children older than 6 months of age. The mean level of anti-lipid A IgM in the acute phase of GNBI and the mean levels of anti-lipid A IgM and IgA in the acute phase of KD were found to increase significantly, in comparison to the age-matched controls. Furthermore, the mean level of anti-lipid A IgA also showed a significant increase from the acute to the subacute phases of KD. Regarding the IgA-subclass response, higher titers of anti-lipid A specific Ab were seen in the IgA2 subclass than in the IgA1 subclass. CONCLUSION: These findings indicate that KD patients demonstrate an intense response to lipid A in the IgA, especially IgA2-subclass, thus suggesting that an unusual activation of the mucosal immune response to a ubiquitous antigen derived from Gram-negative bacteria may be involved in the pathogenesis of KD.     

The majority of children and adolescents with acute myeloid leukemia have detectable anti-DT388-GMCSF IgG concentrations,but at concentrations that should not preclude in vivo activity

PURPOSE: As a novel approach for the treatment of acute myeloid leukemia (AML), the authors are developing a fusion toxin (DT(388)-GMCSF) consisting of a truncated diphtheria toxin (DT(388)) linked to human granulocyte-macrophage colony-stimulating factor (GMCSF). A critical step in the development of DT(388)-GMCSF for clinical use in childhood and adolescent AML is to determine whether children and adolescents have preexisting antibodies to DT(388)-GMCSF due to childhood immunizations against diphtheria toxoid. PATIENTS AND METHODS: Sera from 33 children and adolescents with AML and one with juvenile myelomonocytic leukemia were collected. The median age was 11.8 years. All scheduled diphtheria toxoid vaccinations were current except for the child diagnosed at 4 months of age. Anti-DT(388)-GMCSF antibody concentrations were detected by an enzymoimmunoassay and by an in vitro bioassay. RESULTS: Thirty of 34 (88%) children and adolescents had detectable anti-DT(388)-GMCSF IgG antibody concentrations. The median concentration was 1.5 microg/mL, with a range from undetectable to 191.4 microg/mL. There was a positive correlation between the enzymoimmunoassay and bioassay. There was no difference between the anti-DT(388)-GMCSF IgG concentrations in these children and adolescents with AML and in 43 adults with AML. Preliminary results of the phase 1 trial of DT -GMCSF in adults with AML indicate that patients with baseline anti-DT(388)-GMCSF IgG concentrations of less than 2 microg/mL can achieve circulating DT(388)-GMCSF concentrations and can exhibit antileukemic activity. Twenty-three of 34 (67.6%) children and adolescents had anti-DT(388)-GMCSF IgG concentrations less than 2 microg/mL. CONCLUSIONS: Despite routine diphtheria toxoid vaccinations, most children and adolescents with AML do not have anti-DT -GMCSF IgG concentrations that preclude in vivo activity of DT -GMCSF.     

Regulation of CD31 expression and interleukin-4 production by human cord blood CD4+ T cells with interleukin-4 and interleukin-7

BACKGROUND: T helper 2 cell type cytokines, such as interleukin (IL)-4 and IL-5, play pivotal roles in the development of allergic diseases. However, the mechanism by which naive CD4+ T cells acquire the ability to produce these cytokines remains unclear. Recently, it was reported that IL-7 induces the ability to produce IL-4 as well as interferon (IFN)-gamma and IL-5 in naive CD4+ T cells without TCR stimulation. To further analyze the mechanism of acquiring IL-4-producing ability by naive CD4+ T cells, the effects of IL-7 on human cord blood CD4+ T cells were compared with those of IL-4, which induced the ability to produce IFN-gamma but not IL-4. RESULTS: Interleukin-7 preserved the population of CD4+CD31- T cells in cord blood and induced their IL-4-producing ability without T cell receptor (TCR) stimulation, while IL-4 induced CD31 on CD31- T cells and could not induce their IL-4-producing ability. Both the CD31-inducing effect and the inhibitory priming effect for IL-4-production by IL-4 were also observed after cord blood CD4+ T cells had been primed with IL-7 and acquired the IL-4-producing ability. CONCLUSIONS: Interleukin-7 induced the IL-4-producing ability in naive CD4+CD31- T cells without TCR stimulation, suggesting that the signal transduction via CD31 may have an inhibitory effect on the acquisition of the IL-4-producing ability by cord blood CD4+ T cells in the absence of TCR stimulation.