يعرض 1 - 10 نتائج من 10 نتيجة بحث عن '"Helen K. W. Law"', وقت الاستعلام: 1.23s تنقيح النتائج
  1. 1

    المصدر: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 25(3)

    الوصف: Cord blood (CB) is an alternative stem cell source for allogeneic hematopoietic stem cell transplantation (HSCT). The unique advantages of using CB as a stem cell source are a degree of permissibility for HLA mismatch, rapid availability, and relatively risk-free cell collection. Because HLA is highly polymorphic and population-specific, optimal HLA-matched unrelated donors or cord blood units (CBUs) might not be available. In view of the possibility that matched CBUs that include noninherited maternal antigens (NIMAs) might contain acceptable HLA mismatches, we attempted to determine the degree of alloreactivity of CB mononuclear cells (MNCs) on stimulation by the maternal, paternal, and unrelated stimulator cells. Suppression of T cell proliferation, cytotoxicity, and a cytokine profile indicating suppressed Th1 and elevated IL-10 and TGF-β1 responses were observed in the mixed lymphocyte reaction in response to NIMAs. The increases in IL-10 and TGF-β1 production may be due to the Th2 response and/or regulatory T cells (Tregs). The reduced IL-10 and TGF-β1 production after CD25 depletion could have been due to removal of Tregs from the CB cells. Thus, Tregs appear to play an important role in the CB MNC response to NIMAs, possibly due to the induction of IL-10 and TGF-β1. We hope that our work can provide some evidence of the beneficial effect of NIMAs.

  2. 2

    المؤلفون: Enmei Liu, Helen K. W. Law, Yu-Lung Lau

    المصدر: World Journal of Pediatrics. 6:132-140

    الوصف: As one of the first infectious challenges of life, the impact of neonatal Mycobacterium bovis bacillus Calmette-Guerin (BCG) vaccination on the polarization of neonatal T helper subset has not been well defined.We investigated the effect of BCG-treated cord blood (CB) dendritic cells (DCs) on naïve CD4+ T cells polarization compared with that of adult blood DCs.BCG-treated CB DCs had significantly lower expression of CD83 and a higher ratio of CD47/Fas than BCG-treated adult blood DCs. BCG induced significantly lower IL-12 but relatively higher IL-10 production from CB DCs than adult blood DCs. Moreover, in comparison with BCG-treated adult blood DCs, BCG-treated CB DCs induced higher IL-10 production and cytotoxic T-lymphocyte antigen 4 (CTLA-4) expression, and lower interferon-gamma (IFN-gamma) production from naïve CD4+ T cells. On the other hand, lipopolysaccharide-treated CB DCs had similar capacity as prime naïve CD4+ T cells did to produce higher IFN-gamma, lower IL-10 production, and CTLA-4 expression compared with their adult counterparts.These results suggested that BCG-treated CB DCs might be semi-mature DCs which polarize naïve T cells into a tolerogenic T cell phenotype in newborns.

  3. 3

    المؤلفون: Enmei Liu, Helen K. W. Law, Yu-Lung Lau

    المصدر: British Journal of Haematology. 126:517-526

    الوصف: Allogeneic cord blood (CB) transplantation is associated with less severe graft-versus-host disease (GvHD), thought to be due to the immaturity of CB T cells, but how T cells interact with host and donor-derived dendritic cells (DCs) to initiate GvHD has not been elucidated. We therefore investigated the responses of CB and adult blood CD4(+) T cells co-cultured with adult host DCs of different maturities. Primed by adult host DCs, CB and adult blood CD4(+) T cells underwent similar changes in the expression of CD45RA/45RO, CD25, CD40L and CTLA-4. However, CB CD4(+) T cells, when primed by either immature or Bacillus Calmette-Guerin mycobacteria-treated adult host DCs, produced lower interferon-gamma (IFN-gamma) and higher interleukin-10 (IL-10), which is a regulatory T cell-like cytokine profile, as compared with adult blood CD4(+) T cells. In contrast, lipopolysaccharide (LPS)-treated adult host DCs significantly up-regulated IFN-gamma and down-regulated IL-10 production levels from CB CD4(+) T cells to that from adult blood CD4(+) T cells. The sustained low IFN-gamma and high IL-10 production from CB CD4(+) T cells co-cultured with adult blood DCs might account for the less severe GvHD occurrence after CB transplantation, which could be reversed by LPS-treated adult blood DCs.

  4. 4

    المؤلفون: Yu-Lung Lau, Helen K. W. Law, Enmei Liu

    المصدر: Pediatric Research. 54:105-112

    الوصف: Mycobacterium bovis bacillus Calmette-Guerin (BCG) is given to millions of neonates in developing countries as a vaccine against Mycobacterium tuberculosis; however, little is known about the initiation of response in neonatal dendritic cells (DCs) to BCG. To address this issue, the interaction of BCG with human cord blood monocyte-derived DCs was studied. We showed that BCG could promote cord blood monocyte-derived DC maturation by up-regulation of CD80, CD83, CD86, CD40, and MHC class II molecules and down-regulation of mannose receptor. BCG was able to induce similar levels of tumor necrosis factor-alpha and IL-10 but no bioactive IL-12p70 production from cord blood DCs as from adult blood DCs. Functionally BCG-treated cord blood DCs had higher ability to induce mixed lymphocyte reaction than non-BCG-treated cord blood DCs. Both non-BCG-treated and BCG-treated cord blood DCs efficiently induced a high level of IL-10, medium level of interferon-gamma, but little IL-4 production by cord blood naïve CD4+ T cells. Heat shock protein 65, a key component of BCG, had no effect on cord blood DC maturation in terms of CD86, MHC class II, and mannose receptor up-regulation. During the BCG-induced maturation process of cord blood DCs, nuclear transcription factor Rel-B was up-regulated and cytosolic Rel-B down-regulated with cytosolic IkappaB alpha and beta degradation. These results suggest that BCG can promote cord blood monocyte-derived DC maturation, and that the mechanism is through the up-regulation of nuclear Rel-B secondary to the degradation of cytosolic IkappaB alpha and beta.

  5. 5

    المصدر: Pediatric Research. 50:184-189

    الوصف: Neonates are relatively immature in their immune response; thus, to further clarify the differences of monocyte function and differentiation between neonates and adults, we investigated their CD14(+)CD4(+) and CD14(+)CD16(+) monocyte subpopulations, production of IL-1beta and tumor necrosis factor-alpha induced by lipopolysaccharide, and their CD14 and CD1a phenotypic changes in response to IL-4 and granulocyte-macrophage colony-stimulating factor. Our results showed that 1) the expression of CD14 in cord blood monocytes was significantly lower than that in adult peripheral blood monocytes; 2) both the percentages of CD14(+)CD4(+) cells and CD14(+)CD16(+) cells among CD14(+) monocytes were also significantly lower in cord blood; 3) after stimulation by lipopolysaccharide for 72 h, production of both IL-1beta and tumor necrosis factor-alpha was lower in cord blood than that in adult peripheral blood; and 4) in response to IL-4 or GM-CSF, the phenotype development of CD14 and CD1a in cord blood and adult peripheral blood was different. Down-regulation of CD14 expression in response to IL-4 and GM-CSF was slower in cord blood monocytes than that in adult peripheral blood monocytes. After 9 d of culture in the presence of IL-4 and GM-CSF, the percentage of CD1a(+) monocytes was significantly more increased in cord blood than that in adult peripheral blood. The reduced expression of CD14 and other mature phenotype markers such as CD16 and CD4 as well as the reduced IL-1beta and tumor necrosis factor-alpha production may contribute to the impaired immune response of neonates. Slower down-regulation of CD14 by IL-4 and GM-CSF suggests that differential properties of cord blood monocytes in response to cellular stress signals take a longer time than those of adult peripheral blood monocytes.

  6. 6

    المصدر: British Journal of Haematology. 113:240-246

    الوصف: Dendritic cells are critical for the induction of both primary immune responses and immunological tolerance, as well as for the regulation of T-helper 1 (Th1) and 2 (Th2) immune responses. As neonates are notably deficient in Th1 response and cord blood transplantation is noted to result in less graft-versus-host disease (GvHD), we compared the phenotypic and functional characteristics of monocyte-derived dendritic cells (DCs) that favour Th1 development from cord blood and adult peripheral blood to understand the underlying mechanisms of these observations. Our results showed that: (1) after culture for 7 d with interleukin (IL)-4 and granulocyte--macrophage colony-stimulating factor (GM-CSF), cord blood monocytes generated less CD1a(+) cells than adult peripheral blood monocytes, and the CD1a+ cell percentage decreased thereafter; (2) compared with adult blood DCs, cord blood DCs had reduced intensity of expression of CD1a and MHC class II molecules, but the expression levels of CD11c and CD86 were similar; (3) the endocytotic ability of cord blood DCs was reduced compared with adult blood DCs, and this function was related to reduced mannose receptor (MR)-positive cells; (4) furthermore, the ability of cord blood DCs to stimulate CD3(+) T cells in an allogeneic mixed lymphocyte reaction was significantly lower than that of adult blood DCs. These results suggested that the dysfunction of cord blood monocytes in differentiating into professional DCs will affect the activation of naive T cells, especially Th1 development, and may be related to the susceptibility to different infections in the neonates, as well as the lower incidence of GvHD in cord blood transplantation.

  7. 7

    المصدر: Human immunology. 75(4)

    الوصف: Background Epstein–Barr virus (EBV) is a tumorigenic virus which has effectively infected nearly all human beings with over 95% adult being seropositive. The persistence of latent EBV infection is not fully understood. Recent studies point towards a hypothesis of immune suppression and immune evasion involving regulatory T cells (Tregs) and dendritic cells (DCs). We sought to explore the mechanism of EBV suppression and immune evasion. Methods We compared the effects of EBV on cord blood (CB) and adult DCs differentiation and maturation including phenotype by flow cytometry, cytokine by ELISA and RT-PCR. And we evaluated the function of DC by co-culture DC and Treg by detection the expression of Foxp3, the phenotype and the cytokine profile of Tregs by flow cytometry. Results CB DCs derived from EBV-infected CB monocytes or from EBV-infected CB immature DCs (iDCs) displayed distinct phenotypes of “semi-mature” DCs with high expression of co-stimulatory molecules, such as CD40, CD80 and CD86 but low cytokine production, related to immune tolerance and homeostasis. While the EBV-infected adult iDCs resemble that of “pathogen-driven regulatory mature DCs” with high expression of co-stimulatory molecules, down-regulation of IL-12 secretion and up-regulation of IL-10 secretion, related to protection of host and immune evasion of pathogens. EBV infected cord blood monocytes-derived DCs drived Tregs development by driving the expression of Foxp3, increasing the expression of CTLA-4, decreasing the expression of GITR and promoted the generation of intracellular IL-2 and IL-10 by Tregs. Conclusion Epstein–Barr virus induces the differentiation of semi-mature dendritic cells from cord blood monocytes. The differences between CB and adult DCs suggested that the developmental maturity of the cells may affect their immune responses to EBV infection.

  8. 8

    المصدر: BMC Immunology
    BMC Immunology, Vol 10, Iss 1, p 35 (2009)
    BMC immunology, 10(1):35

    الوصف: Background: The SARS outbreak in 2003 provides a unique opportunity for the study of human responses to a novel virus. We have previously reported that dendritic cells (DCs) might be involved in the immune escape mechanisms for SARS-CoV. In this study, we focussed on the gene expression of toll-like receptors (TLRs), chemokine receptors (CCRs) and death receptor ligands in SARS-CoV infected DCs. We also compared adult and cord blood (CB) DCs to find a possible explanation for the age-dependent severity of SARS. Results: Our results demonstrates that SARS-CoV did not modulate TLR-1 to TLR-10 gene expression but significantly induced the expression of CCR-1, CCR-3, and CCR-5. There was also strong induction of TNF-related apoptosis-inducing ligand (TRAIL), but not Fas ligand gene expression in SARS-CoV infected DCs. Interestingly, the expressions of most genes studied were higher in CB DCs than adult DCs. Conclusion: The upregulation of chemokines and CCRs may facilitate DC migration from the infection site to the lymph nodes, whereas the increase of TRAIL may induce lymphocyte apoptosis. These findings may explain the increased lung infiltrations and lymphoid depletion in SARS patients. Further explorations of the biological significance of these findings are warranted. © 2009 Law et al; licensee BioMed Central Ltd.
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  9. 9

    المصدر: BMC Immunology, Vol 9, Iss 1, p 74 (2008)
    BMC Immunology

    الوصف: Background: The functional immaturity of T cells contributes to the susceptibility of neonates to infections and the less severe graft-versus-host disease associated with cord blood (CB) transplantation. We have previously reported that insulin-like growth factor - I (IGF-I) promotes the phytohaemagglutinin (PHA)-induced CB T cell maturation and inhibits their apoptosis in mononuclear cell (MC) culture. We hypothesized that the effects of IGF-I may be mediated by accessory cells and soluble factors. Results: This study showed that the kinetics of PHA-induced maturation in purified CD3+ T cell was delayed compared to that in CBMC. The addition of autologous CD14+ monocytes increased T cell maturation and potentiated the effect of IGF-I. The addition of IL-6 had no effect on CB T cell maturation but it reduced PHA-induced apoptosis significantly. We further demonstrated that the neutralisation of IL-6 in CBMC culture partially abrogated the anti-apoptotic effect of IGF-1 on T cells. The anti-apoptotic effect of IL-6 was not mediated via the reduction of Fas expression in T cell subsets. Conclusion: Our results suggested that the maturation effect of IGF-1 is partially mediated by monocytes and the anti-apoptotic effect in part via IL-6. Further investigation is needed to explore the therapeutic use of IGF-I in enhancing neonatal immunity. © 2008 Law et al; licensee BioMed Central Ltd.
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  10. 10

    المؤلفون: Yu-Lung Lau, Helen K. W. Law

    المصدر: Experimental Hematology. 28:75

    الوصف: Insulin-like growth factor-I (IGF-I) has been shown to enhance the PHA-induced increase in telomerase activity for cord blood (CB) mononuclear cells. It is hypothesized that the IGF-I on telomerase activity may have an impact on the telomere length and replicative potential of cells. In this study, we have cultured isolate CB T cells (CD3+ purity = 98%) in a similar serum free liquid medium containing: (a) NoGF; (b) IGF-I, (c) PHA, and (d) IGF-I + PHA. The telomere length of cells harvested on Day 0, 3, 5, 8, 14 and 21 was measured by a quantitative flow cytometry based fluorescence in situ hybridisation technique (Q-Flow FISH). The corresponding telomerase activity was determined by the non-radioactive PCR-based Telomeric Repeat Amplification Protocol (TRAP). The telomere length of PHA stimulated T cells increased to a peak level on Day 8 and decreased back to the initial level by Day 21. The addition of IGF-1 increased the telomere length of PHA stimulated T cells throughout the course of the culture. Interestingly, this later increase in telomere length was not accompanied by a high level of telomerase in the cells at later time points in the culture. The heterogeneous relationship between telomerase and telomere length suggested that the effect of IGF-I on telomere length elongation may be due to the involvement of alternative pathways other than the initial enhancement in telomerase activity in the cells. Further experiments are needed to clarify the mechanisms involved and the impact on replicative potential of cells. This data may be useful for the ex vivo expansion of T cells for adoptive immunotherapy and transplantation.