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

The increased susceptibility of neonates to infections has been ascribed to the immaturity of their immune system. More particularly, T cell-dependent responses were shown to be biased towards a Th2 phenotype. Our studies on the in vitro maturation of umbilical cord blood T cells suggest that the Th2 bias of neonatal response cannot be simply ascribed to intrinsic properties of neonatal T cells. Phenotypically, neonatal CD4+ T cells are more immature than their adult CD45RO-/RA+ naive counterparts and they contain a subset (10-20%) of CD45RO-/RA+ CD31- cells which is very low in adults and displays some unique functional features. The activation and maturation of neonatal CD4+ T cells is particularly dependent upon the strength of CD28-mediated cosignal which dictates not only the cytokine profile released upon primary activation but also the response to IL-12. Activation of adult as well as neonatal CD4+ T cells in the context of low CD28 costimulation yields to the production of low levels of only one cytokine, i.e. IL-2. In contrast, strong CD28 costimulation supports the production of high levels of type 1 (IL-2, IFN gamma and TNF beta) and low levels of type 2 (IL-4 and IL-13) cytokines by neonatal T cells. The low levels of naive T cell-derived IL-4 are sufficient to support their development into high IL-4/IL-5 producers by an autocrine pathway. The ability of IL-12 to prime neonatal CD4+ T cells for increased production of IL-4 (in addition to IFN gamma) is observed only when CD28 cosignal is minimal. Under optimal activation conditions (i.e. with anti-CD3/B7.1 or allogenic dendritic cells) the response and the maturation of neonatal and adult naive T cells are similar. Thus the Th2 bias of neonatal immune response cannot be simply ascribed to obvious intrinsic T cell defect but rather to particular conditions of Ag presentation at priming. Unlike CD4+ T cells, neonatal CD8+ T cells strictly require exogenous IL-4 to develop into IL-4/IL-5 producers. Most importantly, anti-CD3/B7-activated neonatal CD8 T cells coexpress CD4 as well as CCR5 and CXCR4 and are susceptible to HIV-1 infection in vitro.
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PMID:Maturation of human neonatal CD4+ and CD8+ T lymphocytes into Th1/Th2 effectors. 971 81

Monocyte-derived dendritic cells (DCs) were used as an in vitro model of myeloid DCs in order to determine a minimum marker pattern with which to characterize and distinguish different stages of DC activation and maturation. Phenotypic changes induced on immature DCs by two prototypic stimuli, poly I:C and CD40 ligation, were first examined. Both elicited HLA-DR, CD40, CD86 and CXCR4 upregulation, and CCR5 downregulation, but only CD40 ligand-stimulated DCs became CD83(+)\CCR7(+), whereas poly I:C-stimulated DCs expressed lower CD83 levels and were mostly CCR7(--). CD40 ligation and poly I:C elicited increased production of inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor-alpha, of IL-10 and the CCL5 chemokine, but profiles differed as to higher IL-10, IL-12 and CCL22 (a CCR4 ligand important for T cell recruitment) levels for the former, and of CCL4 and CCL5 for the latter. Thus, a limited set of phenotypic markers, cytokine and chemokine production assays, may be used to distinguish the three stages in the life of DCs: immaturity, activation and full maturation. The ability of purified protein derivative-loaded DCs to stimulate autologous T cells to produce IL-2, IL-4 and interferon-gamma indeed depended on their activation stage and endocytic activity, which decreased upon maturation. We then examined whether ligation of CD4, CCR5 and\or CXCR4, the receptor and coreceptors of human immunodeficiency virus envelope gp120, respectively, affected DC activation or maturation, neither a monoclonal antibody to the gp120-binding site on CD4 nor CCL5 nor CXCL12, the natural ligands of CCR5 and CXCR4, respectively, nor gp120 altered the DC activation and maturation processes.
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PMID:Double-stranded RNA stimulation or CD40 ligation of monocyte-derived dendritic cells as models to study their activation and maturation process. 1531 72

Respiratory syncytial virus (RSV) infects and causes disease in infants and reinfects with reduced disease throughout life without significant antigenic change. In contrast, reinfection by influenza A virus (IAV) largely requires antigenic change. The adaptive immune response depends on antigen presentation by dendritic cells (DC), which may be too immature in young infants to induce a fully protective immune response against RSV reinfections. We therefore compared the ability of RSV and IAV to activate primary human cord blood (CB) and adult blood (AB) myeloid DC (mDC). While RSV and IAV infected with similar efficiencies, RSV poorly induced maturation and cytokine production in CB and AB mDC. This difference between RSV and IAV was more profound in CB mDC. While IAV activated CB mDC to some extent, RSV did not induce CB mDC to increase the maturation markers CD38 and CD86 or CCR7, which directs DC migration to lymphatic tissue. Low CCR7 surface expression was associated with high expression of CCR5, which keeps DC in inflamed peripheral tissues. To evaluate a possible inhibition by RSV, we subjected RSV-inoculated AB mDC to secondary IAV inoculation. While RSV-inoculated AB mDC responded to secondary IAV inoculation by efficiently upregulating activation markers and cytokine production, IAV-induced CCR5 downregulation was slightly inhibited in cells exhibiting robust RSV infection. Thus, suboptimal stimulation and weak and mostly reversible inhibition seem to be responsible for inefficient mDC activation by RSV. The inefficient mDC stimulation and immunological immaturity in young infants may contribute to reduced immune responses and incomplete protection against RSV reinfection.IMPORTANCE Respiratory syncytial virus (RSV) causes disease early in life and can reinfect symptomatically throughout life without undergoing significant antigenic change. In contrast, reinfection by influenza A virus (IAV) requires antigenic change. The adaptive immune response depends on antigen presentation by dendritic cells (DC). We used myeloid DC (mDC) from cord blood and adult blood donors to evaluate whether immunological immaturity contributes to the inability to mount a fully protective immune response to RSV. While IAV induced some activation and chemokine receptor switching in cord blood mDC, RSV did not. This appeared to be due to a lack of activation and a weak and mostly reversible inhibition of DC functions. Both viruses induced a stronger activation of mDC from adults than mDC from cord blood. Thus, inefficient stimulation of mDC by RSV and immunological immaturity may contribute to reduced immune responses and increased susceptibility to RSV disease and reinfection in young infants.
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PMID:Lack of Activation Marker Induction and Chemokine Receptor Switch in Human Neonatal Myeloid Dendritic Cells in Response to Human Respiratory Syncytial Virus. 3148 54