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)

Very low immunoglobulin secretion occurs in pokeweed mitogen (PWM) stimulated cord blood mononuclear cells (MNC) and has been attributed to an 'immaturity' of both T and B cells of the newborn. The cord blood T cells are phenotypically 'naive' cells, in which suppressor activity for B cell function appears to dominate over helper activity. The cord blood B cells, in spite of their expression of different membrane immunoglobulin isotypes, secrete almost no IgG and IgA in the various B cell assays so far compared. We found that cord blood B cells are as competent as B cells from adults to generate clonal IgM, IgG and IgA responses in a culture system in which a cell contact with mutant EL-4 thymoma cells in conjunction with T cell supernatant leads to strong B cell activity. As regarding the possible causes of the low cord blood PWM response, we studied the role of transforming growth factor-beta 1 (TGF-beta 1), a potent inhibitor of lymphocyte functions. TGF-beta 1 sensitivity of B cells and TGF-beta 1 mRNA levels in MNC were found to be similar for adult and cord blood cells. A neutralizing anti-TGF-beta 1 antibody enhance the adult PWM response, but the immunoglobulin secretion in cord MNC remained very low. We conclude that suppression by endogenous TGF-beta 1 occurs in the PWM system but is not responsible for the low immunoglobulin response of cord blood MNC and that the newborn's B cell 'immaturity' can be overcome with potent T cell signals in vitro. This is consistent with the newborn's capacity to generate a T-dependent B cell response in vivo.
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PMID:Are cord blood B cells functionally mature? 204 18

Hematopoiesis is developmentally immature in the newborn compared with the adult. Diminished gene expression of several positive hematopoietic regulators has been observed in activated cord compared with adult peripheral blood mononuclear cells (MNC; Cairo et al. Pediatr Res, 30:362, 1991 and Cairo et al, Pediatr Res, 31:574, 1992). However, altered expression of negative hematopoietic regulators during states of increased demand may also contribute to the pathogenesis of newborn dyshematopoiesis. To test this hypothesis, we measured protein levels of transforming growth factor-beta 1 (TGF-beta 1) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) in the conditioned media of human umbilical cord and adult MNC using specific enzyme-linked immunosorbent assays. There was significantly less TGF-beta 1 in culture supernatants of cord versus adult MNC after 24, 72, and 120 hours of stimulation (P < .05), and significantly less MIP-1 alpha in cord versus adult supernatants after 72 hours and 120 hours of stimulation (P < .01). We then examined the mRNA expression of the negative regulators TGF-beta 1, MIP-1 alpha, and interleukin-8 (IL-8) in cord and adult MNC using Northern blot hybridization followed by quantitative densitometry. Cord MNC expressed significantly less TGF-beta 1 mRNA than adult MNC 6 hours and 72 hours after stimulation (P < .001). Cord MNC expressed significantly less MIP-1 alpha mRNA than adult MNC 6 hours (P < .01), 24 hours (P < .001), and 72 hours after stimulation (P < .001). Cord MNC also expressed significantly less IL-8 mRNA than adult MNC 6 hours after stimulation (P < .001). Therefore, decreased mRNA accumulation appears to coincide with reduced cytokine expression in the activated cord MNC. There were no significant differences in the transcription rates determined by nuclear run-on assay of either the TGF-beta 1 or MIP-1 alpha gene in cord versus adult MNC after 6 hours of stimulation, suggesting that the reduced TGF-beta 1 and MIP-1 alpha mRNA in activated cord MNC may be secondary to alteration in posttranscriptional regulation. The present results, together with those of our previous studies, suggest that the altered expression of both positive and negative hematopoietic regulators may be involved in the immaturity of host defense in human neonates.
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PMID:Transforming growth factor-beta 1, macrophage inflammatory protein-1 alpha, and interleukin-8 gene expression is lower in stimulated human neonatal compared with adult mononuclear cells. 801 11

Dendritic cells (DC) have important functions in T cell immunity and T cell tolerance. Previously, it was believed that T cell unresponsiveness induced by immature DC (iDC) is caused by the absence of inflammatory signals in steady-state in vivo conditions and by the low expression levels of costimulatory molecules on iDC. However, a growing body of evidence now indicates that iDC can also actively maintain peripheral T cell tolerance by the induction and/or stimulation of regulatory T cell populations. In this study, we investigated the in vitro T cell stimulatory capacity of iDC and mature DC (mDC) and found that both DC types induced a significant increase in the number of transforming growth factor (TGF)-beta and interleukin (IL)-10 double-positive CD4(+) T cells within 1 week of autologous DC/T cell co-cultures. In iDC/T cell cultures, where antigen-specific T cell priming was significantly reduced as compared to mDC/T cell cultures, we demonstrated that the tolerogenic effect of iDC was mediated by soluble TGF-beta and IL-10 secreted by CD4(+)CD25(-)FOXP3(-) T cells. In addition, the suppressive capacity of CD4(+) T cells conditioned by iDC was transferable to already primed antigen-specific CD8(+) T cell cultures. In contrast, addition of CD4(+) T cells conditioned by mDC to primed antigen-specific CD8(+) T cells resulted in enhanced CD8(+) T cell responses, notwithstanding the presence of TGF-beta(+)/IL-10(+) T cells in the transferred fraction. In summary, we hypothesize that DC have an active role in inducing immunosuppressive cytokine-secreting regulatory T cells. We show that iDC-conditioned CD4(+) T cells are globally immunosuppressive, while mDC induce globally immunostimulatory CD4(+) T cells. Furthermore, TGF-beta(+)/IL-10(+) T cells are expanded by DC independent of their maturation status, but their suppressive function is dependent on immaturity of DC.
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PMID:Immunosuppression induced by immature dendritic cells is mediated by TGF-beta/IL-10 double-positive CD4+ regulatory T cells. 1841 5

Newborn foals are very susceptible to infections by opportunistic pathogens such as Rhodococcus equi. This susceptibility is thought to be due to the immaturity of their immune system, in particular their inability to produce interferon-gamma. This deficiency may result from an insufficiency in accessory signals. We therefore compared monocyte-derived dendritic cells (MoDC) from foals and from adult horses. CD172, MHC-I and MHC-II were generally expressed on more than 90% MoDC from foals and adults. CD1w2(+)CD86(+) cells tended to be less represented in 2-3-week-old foals than in adults. This difference was significant among CD14(-) cells. The percentage of CD14(-)CD1w2(+)CD86(+) cells tended to be increased at 3 months. This suggests that very young foal dendritic cells are quantitatively less mature than their adult counterparts. The expression of IL-1, IL-12, IL-15 and IL-18 mRNA was not different in foal and adult MoDC, but the levels of TNF-alpha, IL-10, MCP-1 and TGF-beta were lower in foal cells. TNF-alpha and IL-10 expression was increased by LPS; TNF-alpha even reached the level of adult MoDC. This may mean that the lack of IFN-gamma in foals is not due to decreased levels of IL-12, IL-15 or IL-18, but rather to lower constitutive levels of TNF-alpha.
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PMID:Young foal and adult horse monocyte-derived dendritic cells differ by their degree of phenotypic maturity. 1934 79