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)

Loxoribine is a potent new immunostimulant with a relatively broad spectrum of immunobiological activities. Both loxoribine and its analogues function as agonists of immune responses in a variety of species, including humans. They upregulate the activity of B cells, T cells, NK cells, macrophages, and LAK cells. Induction of enhanced cytokine secretion has been found to involve IFN-alpha/beta, IFN-gamma, TNF-alpha, TNF-beta, IL-1, IL-6, and the 40 kDa chain of IL-12. Evaluation of in vivo activity has been undertaken only for antibody production, NK cell-mediated cytotoxicity, induction of certain cytokines, and LAK cell-mediated cytotoxicity; all four types of activity are markedly upregulated by loxoribine in vivo. Augmentation of antibody production has been observed for protein, recombinant protein, and synthetic peptide antigens, among others. Because loxoribine and its analogues transmit a T-helper-like signal to antibody-producing B cells, it is a highly effective adjuvant even for synthetic peptides that lack T-cell epitopes, effectively replacing the function of T-helper cells in this milieu. It thus provides an alternative, T-cell-independent vaccination strategy if it becomes desirable to avoid untoward T-cell-mediated effects, or in patients with functional or absolute T-cell deficiency. There are a number of features unique to loxoribine that are highly advantageous under specific circumstances: (1) T cell independence; (2) loxoribine augments antibody responses from an intracellular location (rather than at the surface membrane), independently of protein kinase C involvement; this may be particularly relevant for patients with membrane receptor/signal transduction defects; (3) adjuvanticity of loxoribine is essentially free of cytokine dependency; this may be of particular value for organ transplantation patients whose cytokine-dependent immunity is pharmacologically suppressed; (4) loxoribine bypasses functional immunological immaturity, rendering it particularly useful for vaccines in infants. In preclinical safety studies, the drug has exhibited a relatively benign profile. Phase I clinical studies to date have produced no toxicity higher than grade 1. The drug appears to be quite stable, and compares very favorably in direct evaluations with a number of other immunostimulators. A number of clinical trials have been planned for the future.
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PMID:A new approach to vaccine adjuvants. Immunopotentiation by intracellular T-helper-like signals transmitted by loxoribine. 755 Dec 37

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