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)

Aspirin is the most commonly used analgesic and antiinflammatory agent. In this study, at physiological concentrations, it profoundly inhibited CD40, CD80, CD86, and MHC class II expression on murine, GM-CSF + IL-4 stimulated, bone marrow-derived myeloid dendritic cells (DC). CD11c and MHC class I expression were unaffected. The inhibitory action was dose dependent and was evident at concentrations higher than those necessary to inhibit PG synthesis. Experiments with indomethacin revealed that the effects of aspirin on DC maturation were cyclooxygenase independent. Nuclear extracts of purified, aspirin-treated DC revealed a decreased NF-kappaB DNA-binding activity, whereas Ab supershift analysis indicated that aspirin targeted primarily NF-kappaB p50. Unexpectedly, aspirin promoted the generation of CD11c+ DC, due to apparent suppression of granulocyte development. The morphological and ultrastructural appearance of aspirin-treated cells was consistent with immaturity. Aspirin-treated DC were highly efficient at Ag capture, via both mannose receptor-mediated endocytosis and macropinocytosis. By contrast, they were poor stimulators of naive allogeneic T cell proliferation and induced lower levels of IL-2 in responding T cells. They also exhibited impaired IL-12 expression and did not produce IL-10 after LPS stimulation. Assessment of the in vivo function of aspirin-treated DC, pulsed with the hapten trinitrobenzenesulfonic acid, revealed an inability to induce normal cell-mediated contact hypersensitivity, despite the ability of the cells to migrate to T cell areas of draining lymphoid tissue. These data provide new insight into the immunopharmacology of aspirin and suggest a novel approach to the manipulation of DC for therapeutic application.
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PMID:Aspirin inhibits in vitro maturation and in vivo immunostimulatory function of murine myeloid dendritic cells. 1139 Apr 49

The concept that fetal tissue transplants enjoy an immunologic privilege grounds on the primary immaturity of major histocompatibility complex (MHC) expression. However, experiences in human organ transplantation reveal that the immunogenicity of any graft could be modified by external factors such as ischemia. Consequently, the question arises, whether the process of transplantation modifies the immunogenicity of fetal grafts. In a syngeneic rat model (Lewis), fetal adrenal glands were transplanted into the greater omentum of adult hosts. After harvesting the grafts sequentially, the immunogenicity was evaluated by analyzing the expression and distribution of the MHC classes I and II and were compared with untreated organs of equivalent age. The untreated fetal adrenal gland depicted little immunogenicity. However, compared with age-matched untreated control organs, at 2 wk after transplantation, the grafts demonstrated an increased expression of MHC I and II, upregulated throughout the entire adrenal cortex. No signs of MHC-mediated rejection were found. The upregulation of MHC persisted until the eighth week after transplantation. At 3 months after transplantation the expression of MHC I and II returned to the normal pattern of untreated controls. As this study used a purely syngeneic model, the immunologic changes observed could not be induced by a graft vs. host incompatibility, instead they were caused by experimental factors. The expressions of MHC class I and II was increased at 2 wk, but these proteins did not induce a T-cell mediated rejection or cellular infiltration. In conclusion, these findings question the concept of an immunologic privilege of fetal tissue transplants. Instead, experimental factors may modify the tissue's primary immaturity of its MHC. Further investigations must evaluate, whether the increase in MHC expression will have an impact on the rejection of fetal adrenal grafts in allogeneic hosts.
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PMID:Does the transplantation process modify the immunogenicity of fetal adrenal grafts in rat? 1275 46

Neonatal and adult mice mount distinct responses to allogeneic cells. Injection of neonates with fully allogeneic cells results in lethal graft-vs.-host disease (GVHD), whereas injection of semi-allogeneic (F1) cells leads to lifelong tolerance to the alloantigens, often marked by specific CTL non-responsiveness. In contrast, adults injected with the same number of either cell type become primed and develop vigorous anti-donor CTL activity. One possibility for this differential responsiveness may be developmental immaturity in the CTL arm of the immune system. Recent studies have shown that neonates are capable of mounting mature CTL responses, but only in the presence of strong Th1-promoting agents. Here, we demonstrate that neonates are competent to develop vigorous MHC class I-restricted CTL activity in vivo upon exposure to either fully or semi-allogeneic spleen cells. Specific CTL activity was generated using doses of cells approximately tenfold lower than levels used for the induction of GVHD or tolerance. Thus, the present studies demonstrate that mouse neonates are fully mature in their capacity to develop alloreactive CTL activity, as long as the dose of donor cells is low enough. These results have important implications for the known exposure of human fetuses and infants to small numbers of maternal cells.
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PMID:Neonatal tolerance revisited again: specific CTL priming in mouse neonates exposed to small numbers of semi- or fully allogeneic spleen cells. 1521 38

Neonates are clearly more susceptible to severe disease following infection with a variety of pathogens than are adults. However, the causes for this are unclear and are often attributed to immunological immaturity. While several aspects of immunity differ between adults and neonates, the capacity of dendritic cells in neonates to process and present antigen to CD8+ T cells remains to be addressed. We used human CD8+ T cell clones to compare the ability of neonatal and adult monocyte-derived dendritic cells to present or process and present antigen using the MHC class I pathway. Specifically, we assessed the ability of dendritic cells to present antigenic peptide, present an HLA-E-restricted antigen, process and present an MHC class I-restricted antigen through the classical MHC class I pathway, and cross present cell-associated antigen via MHC class I. We found no defect in neonatal dendritic cells to perform any of these processing and presentation functions and conclude that the MHC class I antigen processing and presentation pathway is functional in neonatal dendritic cells and hence may not account for the diminished control of pathogens.
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PMID:Human neonatal dendritic cells are competent in MHC class I antigen processing and presentation. 1789 97