Expression of and responses to CD2 and CD3 in 18‐month‐old children with and without atopic dermatitis

We hypothesize that atopy is associated with a reduced T‐cell function early in life and an imbalance in cytokine production. The purpose of this study was to investigate the expression of and responses to CD2 and CD3 in children who did or did not develop atopic dermatitis early in life. The expression of CD2 and CD3 was analyzed by flow cytometry, and proliferation of CD2 and CD3 was studied by ³H‐thymidine incorporation in phytohaemagglutinin (PHA)‐ and anti‐CD3‐stimulated peripheral blood mononuclear cells (PBMC) of 18‐month‐old children, 25 with and 29 without atopic dermatitis. Exogenous interleukin (IL)‐2 was added to compensate for possible functional differences in accessory cells. Anti‐CD3‐induced secretion of IL‐4, IL‐5, IL‐6, IL‐10, IL‐13, and interferon‐γ (IFN‐γ) was analyzed by enzyme‐linked immunosorbent assay (ELISA). Atopy was associated with a low proportion of CD2⁺ lymphocytes. Responsiveness to PHA, which activates lymphocytes partly via the sheep erythrocyte receptor, CD2, was reduced in the allergic children. The anti‐CD3‐induced proliferation declined more rapidly with antibody dilution in the allergic than in the non‐allergic children. Atopic dermatitis was associated with high levels of anti‐CD3‐stimulated IL‐5 secretion. The IL‐4/IL‐10 and IL‐4/IFN‐γ ratios were higher in children with elevated total immunoglobulin E (IgE) levels. Skin prick test‐negative children with eczema produced higher levels of IL‐10 than skin prick test‐positive children. In conclusion, atopic children have a reduced T‐cell function. Atopic dermatitis is associated with increased IL‐5 production, while high total IgE levels are associated with high IL‐4/IFN‐γ and IL‐4/IL‐10 ratios.     

Low frequency of CD4+, but not CD8+, T cells expressing interferon‐γ is related to cow's milk allergy in infancy

Low interferon‐γ (IFN‐γ) and tumor necrosis factor‐α (TNF‐α) production in peripheral blood mononuclear cells (PBMC) from patients with atopic dermatitis and food allergy have been reported previously. However, it remains unclear whether the weak cytokine production is caused by the imbalance of specific T‐cell subsets or by dysregulation of T‐cell function. In the present study we investigated the intracellular expression of these cytokines at a single‐cell level to clarify the background of the disruption. Twelve of 27 breast‐fed infants (0.1–8.8 months of age) had challenge‐proven cow's milk allergy (CMA), and 15 infants were studied as a healthy control group. PBMC were stimulated with phorbol 12‐myristate 13‐acetate (PMA) and ionomycin. The frequencies of the cells expressing intracellular IL‐4, IFN‐γ, and TNF‐α were assessed using flow cytometry. In addition, at this time‐point leucocyte subsets from the milk of mothers of these infants were evaluated using light microscopy. A lower number of CD8⁺ T cells and the defective capability of CD4⁺ T cells to express IFN‐γ in infant's peripheral blood co‐existed with a lower number of macrophages in their mother's milk.     

Determination of T‐cell subpopulations and intracellular cytokine production (interleukin‐2, interleukin‐4, and interferon‐γ) by cord blood T‐lymphocytes of neonates from atopic and non‐atopic parents

This report describes the results of a prospective study on immunological markers in cord blood for the prediction of allergic diseases in children. First we evaluated methodological aspects of the flow cytometric technique on cord blood cytokine measurements. Subsequently, the T‐cell subsets and percentage of cytokine‐producing cord blood T‐helper (Th) and T‐suppressor/cytotoxic lymphocytes of neonates from atopic and non‐atopic parents were compared. A group of 33 healthy, full‐term newborn infants of whom 23/33 were at risk for atopy (i.e. having at least one parent with one or more atopic symptoms and positive specific immunoglobulin E [IgE] to at least one common inhalant allergen) was studied. A flow cytometric technique was used to analyze cord blood T‐cell subsets and to determine the percentage of interleukin (IL)‐2‐, IL‐4‐, and interferon‐γ (IFN‐γ)‐producing cord blood Th and T‐suppressor/cytotoxic lymphocytes following stimulation with phorbol 12‐myristate 13‐acetate (PMA) and ionomycin. The percentage of CD3 (T lymphocytes), CD3⁺ CD4⁺ (Th lymphocytes), CD3⁺ CD8⁺ (T‐suppressor/cytotoxic lymphocytes), CD19⁺ (B lymphocytes), CD3⁺ CD4⁺ CD45RO⁺ (memory Th lymphocytes), and CD3⁺ CD4⁺ CD45RA⁺ (naive Th lymphocytes) cells was unrelated to parental atopic status. PMA stimulation augmented the percentage of IL‐2‐ and IFN‐γ‐producing Th and T‐suppressor/cytotoxic lymphocytes, whereas the number of IL‐4‐producing T lymphocytes remained very low or undetectable. No differences in the percentage of IL‐2‐, IL‐4‐ and IFN‐γ‐producing Th and T‐suppressor/cytotoxic lymphocytes were found between neonates from atopic and non‐atopic parents. These results will be re‐evaluated when the atopic status of the children at the age of 1 and 2 years can be assessed.     

Maturation of cytokine‐producing capacity from birth to 1 yr of age

Little is known about the immunologic maturation in the early stages of life. The aim of this study was to investigate maturation of immune system from birth to 1 yr of age and to compare immune functions between mothers and their children. Also the effect of atopy to the immune responses of children was examined. Cord blood samples (n = 228) and peripheral blood samples of children (n = 200) and their mothers (n = 208) 1 yr after birth were collected. Whole blood samples were stimulated for 24 and 48 h with Staphylococcal enterotoxin B (SEB), lipopolysaccharide (LPS) and the combination of phorbol ester and ionomycin (P/I). Production of TNF‐α, IFN‐γ, IL‐5, IL‐8 and IL‐10 was determined using ELISA. Significant mother‐to‐child correlation was detected in cytokine‐producing capacity at the age of 1 yr. TNF‐α (P/I, SEB and LPS stimulation), IFN‐γ (P/I and SEB), IL‐5 (P/I and SEB) and IL‐10 (P/I, SEB and LPS) producing capacity increased from birth to 1 yr of age. In general, stimulated cytokine responses were higher in mothers’ than in children’s blood samples, except in the case of P/I and LPS‐stimulated IL‐8, which were highest at birth. Maternal inhalation atopy was associated with increased cord blood IL‐5 (24 and 48 h) and IL‐10 (48 h) production following P/I stimulation. Also children of food atopic mothers expressed elevated cord blood IL‐10 (48 h, P/I) responses and decreased IFN‐γ/IL‐5 ratio (24 h, P/I). In addition, the production of IFN‐γ (24 and 48 h, P/I) and the IFN‐γ/IL‐5 ratio (24 h and 48 h, P/I) at the age of 1 yr was lower among children with food atopic mothers. In conclusion, our results suggest that both adaptive and innate immune responses increase from birth to 1 yr of age, but are still weak in comparison to adult responses. Cytokine responses of children begin to correlate with those of their mothers during the first year of life. Although only few associations were observed between atopy and cytokine‐producing capacity, our results suggest that children of atopic mothers express T_h2‐polarized cytokine pattern.     

CD4+CD25(high) Treg cells in peripheral blood during remission and exacerbation of allergic asthma in children

Aim: To determine the percentage of CD4⁺CD25^high Treg cells in peripheral blood CD4⁺ T cells of allergic asthmatic children during disease remission and exacerbation. Methods: Peripheral blood mononuclear cells (PBMC) and serum samples were collected from 6‐ to 11‐year‐old children with mild‐to‐moderate allergic asthma (n = 34) and from healthy controls (n = 15). CD4⁺CD25^high T cells in PBMC were detected by flow cytometry. Total and specific IgE in serum were analysed by enzyme‐amplified chemiluminescence, and IL‐2 was measured by ELISA. Results: There was no significant difference in CD4⁺CD25^high T‐cell proportions between asthmatic children in exacerbation and remission as compared with controls. CD4⁺CD25^high T‐cell percentages were not correlated with total and specific IgE. IL‐2 was elevated in both disease remission and exacerbation but did not correlate significantly with CD4⁺CD25^high T‐cell percentages. Conclusion: CD4⁺CD25^high T‐cell proportion in the peripheral blood of total CD4⁺ T cells is not reduced in children with allergic IgE‐mediated asthma and does not differ between disease remission and exacerbation.     

Low levels of interferon‐γ in nasal fluid accompany raised levels of T‐helper 2 cytokines in children with ongoing allergic rhinitis

The T‐helper 2 (Th2) cytokines interleukin‐(IL‐) 4, IL‐5, IL‐6, IL‐10 and the Th1 cytokine IFN‐γ and their associations with eosinophils, eosinophilic cationic protein (ECP) and immunoglobulin (Ig) E were studied in nasal lavage fluid from 60 school children with allergic seasonal rhinitis and 36 nonatopic healthy controls, before and during the pollen season. Eosinophil differential counts and IgE increased significantly in the patients during the pollen season. The eosinophil differential counts, ECP and IgE were all significantly higher during the season than in specimens simultaneously obtained from the nonatopic controls. Before season, the levels of ECP and IgE, but not eosinophils, were significantly higher in the patients than in the controls. During the season the nasal lavage fluid levels of IFN‐γ were significantly lower and the IL‐4/IFN‐γ quotients significantly higher in the allergic than in the control children. In the allergic children, but not in the controls, the nasal fluid levels of the Th2 cytokines IL‐4, IL‐5 and IL‐10 increased during the season, and together with IL‐6, were correlated with the differential counts of eosinophils, and with the levels of ECP and IgE. These findings are compatible with the hypothesis that a deficient release of the Th1 cytokine IFN‐γ plays an important role in the pathogenesis of allergic inflammation. Regardless of whether the defective IFN‐γ secretion is primary or a consequence of suppression by other cytokines, it will in the atopic subjects enhance the release of Th2 cytokines, which in turn will facilitate the development of allergic inflammation.     

Downregulation of CD5 and dysregulated CD8+ T‐cell activation

CD5 is a cell surface molecule that is expressed on most circulating T cells and a small population of B cells, and is involved in modulation of antigen‐specific receptor‐mediated activation. Downregulation of CD5 on CD8⁺ T cells is a poorly understood but increasingly recognized phenomenon that may be associated with dysregulated T‐cell activation. An increased subpopulation of activated CD8⁺ T cells with downregulation of CD5 has recently been described in patients with Epstein–Barr virus‐associated hemophagocytic lymphohistiocytosis (HLH) and familial HLH caused by perforin deficiency and Munc 13‐4 deficiency. These cells were detectable only in the acute phase of HLH, in which patients exhibited hypercytokinemia, and declined progressively after successful treatment in parallel with improvement of systemic inflammation. It is unknown whether CD8⁺ T cells from HLH with other causes have similar profiles. Assessment of CD5 expression on T cells has the potential to assist in the understanding of the diagnosis and pathogenesis of human inflammatory diseases such as HLH.     

Interleukin-15 enhances CD4+ CD45RA+ expression on umbilical cord blood mononuclear cells

The reduced incidence of graft‐vs.‐host disease following umbilical cord blood (CB) transplantation may be related to the functional immaturity of newborn T cells expressing mainly the naive CD45RA phenotype. Expansion of CD4⁺ CD45RA⁺ T cells using cytokines may benefit neonates and infants with human immunodeficiency virus (HIV) infection, as a preferential decline in CD4⁺ CD45RA⁺ cells has been noted as HIV disease progresses. The aim of the study was to investigate the effect of interleukin (IL)‐15, a novel cytokine similar to IL‐2 in biological activities, on CD45RA/RO expression and apoptosis in umbilical cord blood (CB) and adult peripheral blood (APB) mononuclear cells (MNCs). Prior to culture, CB MNCs contained a greater number of CD4⁺ CD45RA⁺ cells and fewer CD4⁺ CD45RO⁺ cells than did APB MNCs. When incubated with RPMI‐1640 containing 10% fetal calf serum for 7 days, the percentage of CD45RA⁺ cells within CD4⁺ T cells (%CD45RA⁺/CD4⁺) significantly decreased compared to that of fresh CB MNCs. IL‐15 exerted a dose‐dependent increase of %CD45RA⁺/CD4⁺ and a corresponding decrease of %CD45RO⁺/CD4⁺ in CB MNCs, an effect not observed with APB MNCs treated with IL‐15. The percentages of CD45RA⁺ and CD45RO⁺ expression within CD8⁺ cells, however, were not influenced by IL‐15, in either CB or APB MNCs. A greater number of CB MNCs underwent apoptosis than did APB MNCs after 7 days of culture in RPMI‐1640 containing 10% fetal calf serum. IL‐15 did not inhibit apoptosis but induced proliferation comparable to that achieved in APB MNCs. The ability of IL‐15 to preferentially enhance the proliferation of CD4⁺ CD45RA⁺ cells in CB MNCs suggests a role for immunomodulative therapy in HIV‐infected newborns and infants.     

TCR α+β+/CD19+ cell–depleted hematopoietic stem cell transplantation for pediatric patients

TCR α⁺β⁺/CD19⁺ cell depletion is an emerging technique for ex vivo graft manipulation in HSCT. We report 20 pediatric patients who underwent TCR α⁺β⁺/CD19⁺ cell–depleted HSCT in four Australian centers. Conditioning regimen was dependent on HSCT indication, which included immunodeficiency (n = 14), Fanconi anemia (n = 3), and acute leukemia (n = 3). Donor sources were haploidentical parent (n = 17), haploidentical sibling (n = 2), or matched unrelated donor (n = 1). Mean cell dose was 8.2 × 10⁸/kg TNC, 12.1 × 10⁶/kg CD34⁺ cells, and 0.4 × 10⁵/kg TCR α⁺β⁺ cells. All patients achieved primary neutrophil and platelet engraftment, with average time to neutrophil engraftment 11 days (range 8‐22) and platelet engraftment 24 days (range 12‐69). TRM at 1 year was 15%. Rate of grade II‐IV aGVHD at 1 year was 20% with no grade III‐IV aGVHD seen. CMV reactivation occurred in 81% of CMV‐positive recipients, with one patient developing CMV disease. Average time to CD4 recovery (>400 × 10⁶/L) was 258 days. Overall survival for the cohort at 5 years was 80%. This report highlights the initial experience of TCR α⁺β⁺/CD19⁺ cell–depleted HSCT in Australian centers, with high rates of engraftment, low rates of aGVHD, and acceptable TRM.     

Interleukin‐6, interleukin‐8, interleukin‐11, and interferon‐γ levels in nasopharyngeal aspirates from wheezing children with respiratory syncytial virus or influenza A virus infection

The differences between respiratory syncytial virus (RSV) and influenza A virus (IFAV) in the pathogenesis of wheezing in young children have not been clearly defined. The aim of this study was to assess the contributions of RSV vs IFAV in the pathogenesis of upper airway inflammation in wheezy young children. We compared interleukin (IL)‐6, IL‐8, IL‐11, and interferon‐γ (IFN‐γ) levels in nasopharyngeal aspirates (NPA) from non‐asthmatic children with respiratory virus infections (RSV in 17 children and IFAV in 13 children), asthmatic children with viral infections (RSV in nine children, IFAV in 10 children), and 22 unaffected healthy children (controls). Levels of IL‐11 in NPA from asthmatic children were significantly higher than those from non‐asthmatic children with RSV infection, and RSV infection enhanced the IL‐11 production in NPA significantly compared to IFAV infection. Nasopharyngeal epithelium from children with RSV infection secreted more IL‐6 than that of children with IFAV infection. There was little difference in the IL‐8 and IFN‐γ levels between asthmatic and non‐asthmatic children with RSV or IFAV infection. In conclusion, asthma enhanced IL‐11 production in RSV infection rather than IFAV infection in early childhood. There was a trend towards greater IL‐6 production in RSV infection compared with IFAV infection.     

High production of interleukin‐10 and interferon‐γ in influenza‐associated MERS in the early phase

Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) occurs in various diseases and pathologies, and the clinical symptoms are not consistent with the impaired region. The mechanism of the region specificity is unclear. We investigated the cytokine profiling in cerebrospinal fluid (CSF) and serum obtained from a child with MERS during influenza infection, and compared them with those of serious another serious type of influenza‐associated encephalopathy. There was no elevation of Interleukin (IL)‐1β, which induces convulsion. The inhibitory cytokines of IL‐10 and IFN‐γ were elevated in the early phase in CSF. Comparing them with other patients, the elevation of the cytokine levels were generally mild. Considering that the prognosis of this MERS case was favorable and high levels of inhibitory cytokines including IL‐10 and IFN‐γ might work to localize the lesion and to prevent sequelae.     

The role of TNF‐α in eosinophilic inflammation associated with RSV bronchiolitis

Choi J, Callaway Z, Kim HB, Fujisawa T, Kim CK. The role of TNF‐α in eosinophilic inflammation associated with RSV bronchiolitis.
Pediatr Allergy Immunol 2010: 21: 474–479.
© 2009 John Wiley & Sons A/S The purpose of our study was to investigate whether tumor necrosis factor (TNF)‐α correlates with eosinophilic inflammation that occurs during a lower respiratory tract infection with the respiratory syncytial virus (RSV) in children. Sixty children with RSV bronchiolitis (RSV group) and 20 healthy children with no respiratory symptoms (Control group) were enrolled. We measured the nasal lavage fluid (NLF) Th2 cytokine (IL‐5), proinflammatory cytokine (TNF‐α, IL‐8), eosinophil‐active cytokine [granulocyte‐macrophage colony stimulating factor (GM‐CSF), IFN‐γ], and eosinophil‐active chemokine (eotaxin, regulated on activation normal T cell excreted and secreted) levels for both groups. We also measured serum eosinophil‐degranulation product (eosinophil‐derived neurotoxin; EDN, eosinophil cationic protein; ECP) levels from RSV group. TNF‐α, IL‐8, GM‐CSF, IFN‐γ, and eotaxin levels were significantly higher in the RSV group compared with the Control group. TNF‐α correlated with GM‐CSF (r = 0.87, p < 0.0001), IFN‐γ (r = 0.92, p < 0.0001), eotaxin (r = 0.64, p < 0.0001), and IL‐8 (r = 0.84, p < 0.0001). TNF‐α may have an important role in eosinophilic inflammation of airways in children with RSV bronchiolitis.     

Munc13‐4 deficiency with CD5 downregulation on activated CD8+ T cells

Familial hemophagocytic lymphohistiocytosis (FHL) is characterized by uncontrolled activation of T cells and macrophages and hypercytokinemia. We have recently described a significant increase in a subpopulation of CD8⁺ T cells with downregulation of CD5 during the acute phase of FHL type2 (FHL2; perforin deficiency), which declines after successful treatment, with a concomitant reduction in serum cytokine level. This unusual subset of CD8⁺ T cells, however, has not been characterized in patients with other subtypes of FHL. Herein, we describe a patient with FHL3 (Munc13‐4 deficiency) carrying compound heterozygous mutations in the UNC13D gene. He had high serum levels of pro‐inflammatory cytokines and significantly increased activated CD8⁺ T cells with downregulation of CD5 during the acute phase, similar to that found in FHL2. This immunophenotypic feature may serve as a useful marker of immune dysregulation in FHL3 in addition to FHL2.     

Visceral leishmaniasis in two patients with IL‐12p40 and IL‐12Rβ1 deficiencies

Mutations of the IL12B and IL12RB1 genes underlie the development of IL‐12 p40 and IL‐12Rβ1 deficiencies, respectively, both of which cause predisposition to infection with weakly virulent mycobacteria and Salmonella. Infections with other intramacrophagic organisms have only been rarely observed. We identified two patients with visceral leishmaniasis who had autosomal recessive IL‐12 p40 and IL‐12Rβ1 deficiencies, respectively. This finding demonstrates the importance of IFN‐γ immunity in the control of leishmaniasis. We also searched the literature for similar reports in patients with these and other primary immunodeficiencies.     

Glucocorticoids enhance interleukin‐4 production to neo‐antigen (hyaluronidase) in children immunocompromised with cytostatic drugs

Immunoglobulin E (IgE)‐mediated immediate‐type allergic reactions to hyaluronidase have been observed in children with central nervous system (CNS) tumors. Glucocorticoids, used as therapy for brain edema, are discussed controversially as T helper 2 (Th2) stimulatory factors. In this study we investigated the role of glucocorticoids on a Th2 cytokine‐promoting effect in children with CNS tumors. Peripheral blood mononuclear cells (PBMCs) from: 29 children suffering from malignant brain tumors, of whom 23 received short‐term glucocorticoid treatment (for 3–4 days) during the course of chemotherapy; 18 children with nephrotic syndrome or renal transplantation receiving long‐term glucocorticoid treatment; and 13 healthy children, were incubated with phytohemagglutinin (PHA) and/or anti‐CD28 monoclonal antibody (mAb) and, in a second approach, with hyaluronidase. The concentrations of Th cell‐mediated cytokines – interleukin (IL)‐4, IL‐10, and interferon‐γ (IFN‐γ) – were measured in supernatants. The IL‐4 production of PBMCs incubated with PHA/anti‐CD28 mAb from children with repeated co‐administration of glucocorticoids, hyaluronidase, and cytostatic drugs (median: 249.9 pg/ml; range: 234.4–261.7) was significantly higher (p < 0.0001) than IL‐4 production of PBMC from children of all the other groups (median: 86.18; range: 16.0–212.5). There was no significant difference in the levels of IL‐10 and IFN‐γ within the groups. PBMCs stimulated only with hyaluronidase failed to produce detectable levels of cytokines. The results of this study indicate that repeated co‐administration of glucocorticoids and hyaluronidase (a neo‐antigen) enhance IL‐4 production in vitro and thus may induce the production of specific IgE antibodies in children immunocompromised with cytostatic drugs. Hyaluronidase itself does not stimulate in vitro IL‐4 synthesis in PBMCs of children receiving cytostatic drugs.     

Peripheral blood biomarkers for the characterization of alloimmune reactivity after pediatric liver transplantation

Individualization of immunosuppressive medications is an important objective in transplantation medicine. Reliable biomarkers to distinguish between patients dependent from intensive immunosuppressive therapy and those where therapy can be minimized among pediatric transplant recipients receiving immunosuppressive medications are still not established. We evaluated the potential of cross‐sectional quantification of regulatory T cells, lymphocyte subsets, and cytokine concentrations as biomarkers in 60 pediatric liver transplant recipients with AR, CR, or normal graft function and in 11 non‐transplanted patients. Transplant recipients presenting with AR had significantly higher CD8⁺ T‐cell counts, significantly higher concentrations of IL‐2, and increased levels of IFN‐γ compared with asymptomatic patients or controls. Regulatory T‐cell numbers did not differ between children with rejection and children with good graft function. A tendency toward increased concentrations of IL‐4 and TGF‐β was detected in transplant recipients with good graft function. Cross‐sectional parameters of peripheral regulatory T cells in pediatric liver transplant recipients do not seem to be valuable biomarkers for individualizing immunosuppressive therapy prior to the weaning process. Lymphocyte subsets, IL‐2, IFN‐γ, IL‐4, and TGF‐β serum concentrations may be helpful to identify children in whom immunosuppression can be reduced or discontinued.     

Involvement of CD5+CD19+Cell in steroid‐dependent nephrotic syndrome treated with B‐cell targeting therapy

We showed in this study the longitudinal changes of the B‐cell counts in patients with steroid‐dependent nephrotic syndrome (SDNS) treated with cyclophosphamide (CPM) and mycophenolate mofetil (MMF). In our case with SDNS, this combined therapy not only decreased B‐cell counts but also increased CD5⁺CD19⁺ (CD5⁺B)/ CD5^‐CD19⁺ (CD5‐B) cell ratio. Recurrence was not observed when an elevated CD5⁺B/CD5‐B cell ratio was maintained even after the B cells increased. Therefore, this ratio might be more important than the whole B‐cell counts. The changes of this ratio could be a good predictor of the clinical course of the patients treated with B‐cell targeting therapy.     

Tracheal aspirate gene expression in preterm newborns and development of bronchopulmonary dysplasia

Background: Bronchopulmonary dysplasia (BPD) occurs in association with prenatal conditions predisposing infants to inflammation and remodeling of the premature lungs. Because of the lack of useful biomarkers for BPD, the gene expression of tracheal aspirate fluid (TAF) cells in premature infants was analyzed. Methods: Of 148 consecutive patients, 26 preterm infants (gestational age <34 weeks) were enrolled, who underwent assisted ventilation at birth for respiratory failure. Patients with congenital disorders were excluded. Half of these infants developed BPD. Interleukin (IL)‐10, interferon (IFN)‐γ, transforming growth factor (TGF)‐β1, and platelet‐derived growth factor (PDGF)‐B mRNA of TAF cells were quantified on real‐time polymerase chain reaction. Results: IL‐10 (P < 0.01) and IFN‐γ (P= 0.03) but not TGF‐β1 or PDGF‐B mRNA levels at birth were higher in BPD than in non‐BPD infants. IL‐10 expression differentiated BPD with the highest sensitivity (92%) and specificity (77%). IL‐10 levels correlated with TGF‐β1 (P= 0.03) and IFN‐γ (P= 0.01), but not with PDGF‐B levels. When BPD infants were classified according to comorbidity (group 1, six patients who suffered respiratory distress syndrome [RDS] but not chorioamnionitis [CAM]; group 2, five patients who had CAM but not RDS), PDGF‐B levels were higher in group 2 (P= 0.01). High IL‐10 expression was selected as a risk factor for BPD in infants who had CAM but not RDS (P= 0.01), although prolonged oxygen therapy was the most sensitive indicator for BPD (P < 0.01) on multivariate analysis. Conclusions: High IL‐10 expression in TAF cells at birth could predict the evolution of BPD, but with less impact than oxygen requirement. PDGF might play a different role in the inflammatory process of premature lungs.     

Immunodeficiency with recurrent panlymphocytopenia,impaired maturation of B lymphocytes,impaired interaction of T and B lymphocytes,and impaired integrity of epithelial tissue: A variant of idiopathic CD4+ T lymphocytopenia?

Idiopathic CD4⁺ T lymphocytopenia (ICL) has been defined as a cause of immunodeficiency with a variable clinical course and an unknown etiology. Here we describe a now 18‐year‐old boy with ICL, chronic mucocutaneous candidiasis (CMC), recurrent abscesses, and relapsing aphthous and ulcerous lesions. In addition to ICL the patient frequently showed a panlymphocytopenia. An increased percentage of γ⁺δ⁺ T lymphocytes and IgD⁺ IgM⁺ B lymphocytes, and a decreased percentage of CD21⁺ B lymphocytes, were observed. In vitro assays showed normal T‐cell responses to candidin and T‐cell mitogens, but impaired B‐cell responses to pokeweed mitogen (PWM). B‐cell maturation after stimulation with Staphylococcus aureus Cowan I (SAC) and interleukin 2 (IL‐2) was nearly normal. The clinical course of the patient improved substantially on administration of constant low‐dose therapy with fluconazole.     

Ex vivo‐expanded donor CD4+ lymphocyte infusion against relapsing neuroblastoma: A transient graft‐versus‐tumor effect

High‐risk neuroblastoma has a poor prognosis despite multimodal treatment including high‐dose chemotherapy. A 7‐year‐old male with neuroblastoma received ex vivo‐expanded donor CD4⁺ T lymphocyte infusion (CD4⁺ DLI) after recurrence in the bone marrow following allogeneic hematopoietic stem cell transplantation from his HLA‐identical mother. The disease transiently responded to CD4⁺ DLI with reduction of tumor cells and a decrease of serum neuron‐specific enolase. The response was associated with development of continued high fever and an increase of cytotoxic T lymphocytes in peripheral blood. This case suggests a possibility of a graft‐versus‐tumor effect against neuroblastoma. Pediatr Blood Cancer 2009;52:895–897. © 2009 Wiley‐Liss, Inc.