Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A study was carried out on cord blood T cell activation via the CD2-mediated pathway. Despite similar percentages of circulating CD3+ and CD2+ cells in adult and cord blood, the proliferation of cord PBMC to the anti-CD3 mAb and cord T cells to anti-CD2 mAb were defective. The T cell CD3-surface structure was normally able to control CD2-mediated activation, as its modulation by a non-mitogenic anti-CD3 mAb blocked cord PBMC proliferation induced by anti-CD2 mAb. CD2-stimulated cord T cells did not proliferate and did not produce a significant amount of IL-2 in culture, although they expressed the IL-2R. This observation was confirmed by the optimal proliferation of CD2-induced cord T cells when rIL-2 was added. Despite the alternative T cell activation pathway is monocyte-independent in adults, the defective cord T cell activation via the CD2 molecule could also be bypassed by the addition of PMA, small amounts of either autologous or allogeneic adult and cord AC or simply rIL-1 alone. Our findings provide evidence for an intrinsic functional defect in cord CD2-mediated T cell activation, which is linked to an impaired increase of free cytoplasmic calcium, as confirmed by the effectiveness of calcium ionophore A23187 in restoring a good CD2-induced cord T cell proliferation and by measurement of cellular calcium uptake after activation via the CD2 molecule. The characteristics of cord T cells revealed by this study recall the thymocyte functional pattern and may represent functional expression of the previously described phenotypic immaturity of cord T cells.
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PMID:Activation of cord T lymphocytes. I. Evidence for a defective T cell mitogenesis induced through the CD2 molecule. 256 56

To extend our studies about phenotypical and functional alterations of G-CSF-induced neutrophils we have evaluated their light-scatter profile, mobilization of intracellular calcium ([Ca2+]i) and membrane depolarization after stimulation. A significant increase in the forward scatter signals could be demonstrated in such neutrophils from patients with neutropenias of various origin and from healthy test subjects. This increase began 4 h and returned to normal 96 h after G-CSF injection in the latter group. We found an impairment of [Ca2+]i mobilization in neutrophils from patients with glycogen storage disease type IB after stimulation of these cells with fMLP. It was even more pronounced than in severe congenital neutropenia (SCN). However, [Ca2+]i fluxes were normal when ionomycin was used. Neutrophils from patients with cyclic neutropenia (cyNP) and chemotherapy-induced neutropenia (chNP) mobilized [Ca2+]i similar to those from healthy donors. Furthermore, we found a decreased percentage of neutrophils depolarizing after stimulation with fMLP and PMA in patients with SCN, whereas membrane depolarization was normal in patients with chNP and cyNP. All the alterations found here are suggested to be caused by a partial immaturity of the neutrophils, although in vivo activation and a direct effect of G-CSF on myeloid precursors might be involved.
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PMID:Changes in light-scatter profile, membrane depolarization and calcium mobilization of neutrophils induced by G-CSF in vivo. 752 31

IgG, IgA, and IgE production by newborn B cells is limited both in vivo and in vitro in various activation conditions, whereas IgM production is readily detectable. It has been suggested that the Ig heavy chain switch inability could be the consequence of T and B cell immaturity. As the interaction between CD40 (expressed on B cells) and its ligand CD40-L (expressed on activated T cells) triggers a key signal required for isotype switching, we studied the expression and function of these two components in normal fetuses, newborns, and infants, compared with adults. CD40-L expression was not inducible in 28 of 30 specimens of newborn cord-blood T cells following incubation with PMA and ionomycin, whereas activation markers such as CD69 were inducible. CD40-L expression was triggered by activation of T cells from infants > 3 wk of age. Surprisingly, T cells from 19- to 28-wk-old fetuses also expressed CD40-L following activation. CD40-L expression on newborn T lymphocytes was induced on T cell lines generated in the presence of PHA and maintained with IL-2 following further stimulation with PMA and ionomycin. CD40-L mRNA transcripts and intracytoplasmic protein expression following activation of newborn T cells were strongly decreased, leading to undetectable protein membrane detection. These results point to a possible transcriptional down-regulation of CD40-L expression by neonatal T lymphocytes. In addition, fetal and cord-blood B cells were poorly able to switch to IgG or IgA by stimulation with CD40 agonists (Ab or soluble CD40-L) in the presence of IL-4 or IL-10 as also detected with surface IgD+ adult B cells. Both phenomena could contribute to the neonatal Ig switch inability, although distinct underlying regulatory mechanisms are probably involved, as suggested by different in vivo time courses.
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PMID:Undetectable CD40 ligand expression on T cells and low B cell responses to CD40 binding agonists in human newborns. 753 Jul 39

The functional immaturity of neonatal alveolar macrophages (AM) may contribute to the increased susceptibility of neonates to lung injury. Because the secretion of proteinases by neonatal AMs may be involved in normal postnatal lung development and in repair after lung injury, we evaluated the capacity of neonatal AMs to secrete 92 kD Type IV collagenase. AMs were obtained by bronchoalveolar lavage from newborn rats at different postnatal ages. Total gelatinase activity was measured by zymography in AM-conditioned media. Spontaneous secretion of gelatinase from AMs varied significantly with age, the highest levels being found immediately after birth. Stimulation of AMs by PMA induced a four- to fivefold greater increase in total gelatinase activity during the first 10 d of postnatal life compared with adulthood. Using [3H]gelatin as the substrate, we found high free gelatinase activity only within 24 h after birth; data obtained after exposing cells to natural surfactant suggested that surfactant may account in part for this increase in free gelatinase activity. No secretion of tissue inhibitor of metalloproteinases (TIMP) by AMs was detectable in newborns within 24 h after birth. We conclude that AMs from newborn rats are able to secrete more gelatinase than AMs from adults, and this enzyme production profile during the neonatal period may contribute to the fact that newborns with lung injury are at high risk for extracellular matrix degradation.
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PMID:Increased 92 kD gelatinase activity from alveolar macrophages in newborn rats. 776 43

Adult and neonatal immunocompetent cells exhibit important functional distinctions, including differences in cytokine production and susceptibility to tolerance induction. We have investigated the molecular features that characterize the immune response of cord blood-derived T lymphocytes compared with that of adult T lymphocytes. Our findings demonstrate that phospholipase C (PLC) isozymes, which play a pivotal role in the control of protein kinase C activation and Ca2+ mobilization, are differently expressed in cord and adult T lymphocytes. PLCbeta1 and delta1 are expressed at higher levels in cord T cells, while PLCbeta2 and gamma1 expression is higher in adult T lymphocytes. PLCdelta2 and gamma2 appear to be equally expressed in both cell types. In addition, a functional defect in PLC activation via CD3 ligation or pervanadate treatment, stimuli that activate tyrosine kinases, was observed in cord blood T cells, whereas treatment with aluminum tetrafluoride (AlF4-), a G protein activator, demonstrated a similar degree of PLC activation in cord and adult T cells. The impaired PLC activation of cord blood-derived T cells was associated with a a very low expression of the Src kinase, Lck, along with a reduced level of ZAP70. No mitogenic response to CD3 ligation was observed in cord T cells. However, no signaling defect was apparent downstream of PLC activation, as demonstrated by the mitogenic response of cord T cells to the pharmacologic activation of protein kinase C and Ca2+ by treatment with PMA and ionomycin. Thus, neonatal cord blood-derived T cells show a signaling immaturity associated with inadequate PLCgamma activation and decreased Lck expression.
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PMID:Inefficient phospholipase C activation and reduced Lck expression characterize the signaling defect of umbilical cord T lymphocytes. 1045 76

The aim of the study was to elucidate the relationship between the cytokine response to staphylococcal enterotoxin A (SEA) at birth and subsequent staphylococcal colonization in the first months of life. In a cohort of 45 newborns, cord blood lymphocytes were stimulated with SEA (10 ng/ml) in vitro, re-stimulated with PMA (phorbol myristate acetate) and ionomycin at day 3 and assessed for CD45RO expression and cytokine generation by flow cytometry. The infants were classified into three groups according to nasal staphylococcal colonization and enterotoxin generation at 3 months: There were 16 infants with either no colonization or non-enterotoxin-producing staphylococci, 16 infants with enterotoxins B, C, D and E, and 13 infants colonized with SEA-producing staphylococci. At birth, the group without subsequent colonization displayed a significantly higher frequency of CD45RO-positive interferon-gamma-producing cells (1.7%; range 0.0-9.3%) in comparison to the SEA-positive group (0.1%; range 0.0-0.4%) and also to the group positive for other enterotoxins (0.50%; range 0.0-2.5%). Comparable but less pronounced results were found for interleukin-5 but not for interleukins 2 and 4. At 6 months, no differences in cytokine generation were detected between the three groups. The results provide evidence that a non-specific immunologic immaturity at birth is a risk factor for early bacterial colonization. Furthermore, it is remarkable that this immaturity is similar to that seen in infants destined to be atopic with respect to disequilibrium of interferon-gamma to interleukin-4 generation. Thus the link between early staphylococcal colonization and subsequent atopy requires further investigation.
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PMID:Infants colonized with enterotoxin-producing staphylococci at 3 months display a decreased frequency of interferon-gamma-producing CD45RO lymphocytes upon stimulation with staphylococcal enterotoxin A at birth but not at 6 months of age. 1067 19