Deficient DR antigen expression on human cord blood monocytes: Reversal with lymphokines (original) (raw)
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British Journal of Haematology, 2001
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 colonystimulating factor (GM-CSF), cord blood monocytes generated less CD1a 1 cells than adult peripheral blood monocytes, and the CD1a 1 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 1 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.
American Journal of Reproductive Immunology, 2013
The aim of our study was to estimate the expressions of both B7-H1 and B7-H4 as well as CD200 and CD200R co-stimulatory molecules on immature myeloid and lymphoid dendritic cells, B CD19 + lymphocytes and monocytes in umbilical cord blood of healthy neonates and in peripheral blood of healthy adults. Method of study Thirty-nine healthy full-term neonates from physiological single pregnancies and 27 healthy adults were included in the study. The expressions of B7-H1, B7-H4, CD200, CD200R antigens were estimated using flow cytometry. Statistical analysis was performed using a non-parametric Mann-Whitney U-test and parametric Wilcoxon's test. Results The expressions of B7-H1 and B7-H4 molecules on immature BDCA-1 + myeloid dendritic cells were significantly lower in umbilical cord blood of healthy neonates when compared with those cells in peripheral blood of healthy adults (P < 0.0001). Furthermore, the suppression of B7-H4 molecule on BDCA-2 + lymphoid dendritic cells was observed in cord blood of healthy neonates when compared with peripheral blood of healthy adults (P < 0.02). The expressions of CD200 antigen on BDCA-1 + cells, CD200R antigen on BDCA-2 + cells and CD200R antigen on B CD19 + cells were significantly lower in cord blood of healthy neonates. On the other hand, the expressions of CD200 and CD200R as well as B7-H4 co-stimulatory molecules on CD14 + cells were significantly higher in cord blood when compared with peripheral blood. Conclusion The increased percentages of CD14 + monocytes with the expressions of CD200 and CD200R as well as B7-H4 co-stimulatory molecules can suggest the increased immunomodulatory properties of neonatal monocytes in cord blood.
International Journal of Gynecology & Obstetrics, 1992
Protection against immune haemolytic disease of newborn infants by maternal monocyte-reactive IgG alloantibodies (anti-HLA-DR) The extent to which maternal anti-Rh(D) antibodies support lysis of erythrocytes by monocytes in the antibody-dependent cellmediated cytotoxicity (ADCC) assay is closely correlated with the severity of Rh(D) haemolytic disease of the newborn infant (HDN). However, in some cases HDN is much milder than would be predicted from the ADCC value. We postulated that maternal ADCC-blocking alloantibodies against paternal antigens on monocytes can protect these infants against severe haemolysis. We studied 13 severely Rh(D)-alloimmunised mothers whose infants showed unexpectedly mild HDN (group I) and 14 women with similar ADCC values but whose infants had severe HDN (group II). 7 group-I women had monocyte-reactive IgG alloantibodies that inhibited lysis by paternal monocytes in the ADCC. No such antibodies were found in group II (p<0·01). In 6 of the 7 serum samples with monocyte-reactive antibodies, the antibodies had HLA-DR specificity. Our findings suggest that Rh(D)-positive children of some severely Rh(D)-alloimmunised women may be protected from severe HDN by maternal non-HLA-class-l, IgG alloantibodies against paternal monocyte blood-group antigens. These antibodies may inhibit the mononuclear phagocyte system of the fetus.
Clinical and Experimental Immunology, 2001
The aim of this study was to investigate the effect of prematurity, neonatal sepsis, respiratory distress syndrome (RDS) and perinatal asphyxia on monocyte HLA-DR expression of neonates using a flow cytometric method based on monocyte negative selection. The subjects were one hundred and thirty-one neonates (59 healthy, 44 septicaemic, 20 with RDS and eight with perinatal asphyxia) and 20 healthy adults. Monocyte HLA-DR expression was measured using one-colour HLA-DR labelling in a gate for monocytes obtained using the combination of CD3-CD19±PE/CD15±FITC MoAbs. In addition, the common dual staining method using MoAbs against two CD14 epitopes (TUK4, MO2) was evaluated. With the one-colour HLA-DR labelling higher purity and recovery values of monocytes were achieved than with the dual labelling method. Healthy neonates had significantly lower percentages of HLA-DR 1 monocytes than adults (69^13% versus 91´5^2´5%) and comparable mean fluorescence intensity (MFI) (119^25 versus 131^26). Values did not differ significantly between healthy term and preterm neonates. Preterm neonates with RDS had a significantly lower percentage of HLA-DR 1 monocytes than the healthy preterm neonates. In neonates with asphyxia both parameters were comparable to those of the healthy ones. Septicaemic neonates presented significantly lower values of both parameters than the healthy, RDS and asphyxiated neonates. Monocyte negative selection provides a reliable estimation of HLA-DR expression on monocytes. Expression of monocyte HLA-DR is lower in healthy neonates in comparison with adults and is further decreased in neonates with sepsis and RDS, but it is not influenced by prematurity and perinatal asphyxia.
Functional Heterogeneity of Human Cord Blood Monocytes
Scandinavian Journal of Immunology, 1984
Human cord blood monocytes were separated into four different subpopulations by means of a discontinuous bovine serum albumin (BSA) gradient. Of the least dense, 31% were present in fraction A, 17% in fraction B and 13% in fraction C and ofthe most dense, 20% were in fraction D. The rest (17%) sedimented as a pellet, of which 93% were dead cells. The monocytes of fraction C (density & 1.070) demonstrated suppressor activity on in vitro antibody synthesis of maternal B cells. Fraction D (density S 1.075) monocytes enhanced antibody synthesis of maternal B cells compared with synthesis produced in a similar experiment with unfractionated monocytes. Addition of either fraction A or B monocytes to the mixed culture of T and B cells resulted in antibody production comparable to that produced by addition of unfractionated monocytes. The functional heterogeneity of the cord monocytes was assayed also by 2-deoxyglucose (2-DOG) uptake, a marker for immunological macrophage activation. Fractions A and D showed significantly higher 2-DOG transport than that of unfractionated monocytes; in contrast, fraction C showed a 50% reduction of 2-DOG uptake. Furthermore, in contrast" to fraction D, fraction C possessed only minimal phagocytic activity (for antibody-coated sheep erythrocytes) and minimal hemoxygenase enzyme activity. These data demonstrate functional heterogeneity of cord blood monocytes.
Human Immunology, 2000
Earlier studies noted that patients who underwent cord blood (CB) transplantation had a lower incidence of graft-versus-host disease (GVHD) than those who underwent bone marrow transplantation (BMT). The premise that the immune reactivity of CB mononuclear cells (CB-MNC) to HLA mismatched combinations and to noninherited maternal antigens (NIMA) may be one of the factors involved in this phenomenon is still debatable. In this study we have attempted to evaluate the alloresponse and alloreactivity induced by CB-MNC by means of the standard mixed lymphocyte reaction test (SMLR) and the more sensitive, modified mixed lymphocyte reaction test (MMLR). Both techniques were used to test CB-MNC (n ϭ 28) against HLA class II mismatched MNC from mothers (n ϭ 26), fathers (n ϭ 12), and unrelated individuals (n ϭ 60) who served as controls. Alloresponse capabilities and stimulation capacities of CB-MNC in the SMLR were similar to those of control MNC: relative response (RR) ϭ 73 vs. 65 and 58 vs. 65, respectively. Similar results were obtained in the MMLR. CB-MNC responded weakly to the maternal MNC in comparison with control MNC (RR ϭ 47 vs. 73 [p ϭ 0.0099]), while a stronger response was noted to the paternal than the maternal MNC (RR ϭ 72 vs. 47 [p ϭ 0.045]). Our results demonstrate that CB-MNC both respond to and induce alloresponse in HLA mismatched combinations. Moreover, the hyporesponse of CB-MNC to maternal cells that we observed suggests a form of tolerance to NIMA, which is probably due to the fetus's exposure to these antigens in its intrauterine life.
Scandinavian Journal of Immunology, 2001
The cellular immune system of the newborn infant is immature and hypo-responsive when compared with adults. The extent to which immaturity of the leucocyte function underlies hyporesponsiveness in the newborn is incompletely understood. In this study flow cytometric techniques were applied to investigate the concurrent expression of a range of surface and intracellular leucocyte functional molecules and cytokines in resting and stimulated cord and adult blood. Production of interleukin (IL)-2 and expression of the components of its receptor, IL-2R alpha/beta/gamma, were investigated. No differences in the proportion of leucocytes producing IL-2R alpha and IL-2R gamma were observed for newborns and adults. A lower proportion of T cells and natural killer (NK) cells from newborns expressed IL-2R beta and upregulation of expression was slower. We hypothesize that reduced IL-2R beta may curtail early autocrine IL-2 activation of immune responses in the newborn. This hypothesis was supported by the observation that an increased proportion of stimulated T cells from newborns produced IL-2 at 4 h poststimulation, but at 24 h the proportion was lower than for adult T cells. The very low levels of interferon (IFN)-gamma produced by neonatal T cells and NK cells may also be partly explained by a curtailment of early autocrine activation of T cells. Expression and kinetics of upregulation for other functional molecules were studied. CD71, HLA-DR, tissue factor and CD152 levels were not significantly different for adults and newborns, suggesting that cord blood leucocytes, in some respects, may demonstrate functional maturity. IL-6 secretion by stimulated monocytes was also comparable in cord and adult blood. However, IL-1 alpha and IL-1 beta were produced by a lower proportion of monocytes from newborns than adults. Similarly, tumour necrosis factor (TNF)-alpha production for monocytes and T cells was lower in cord blood. The mean fluorescence intensity for IL-1 alpha, IL-1 beta and TNF-alpha was also lower for leucocytes from cord blood. These findings are significant in relation to the inability of newborn infants to mount a febrile response to infection. The findings of lower expression of IL-2R beta and lower production of inflammatory cytokines IL-1 alpha, IL-1 beta and TNF-alpha is a basis for improved understanding of the immunological immaturity of leucocytes in the newborn.
Selective developmental defects of cord blood antigen-presenting cell subsets
Human Immunology, 2004
Defective antigen-presenting cell (APC) function has been hypothesized to contribute to increased infection susceptibility in newborns. We used multiparameter flow cytometry to characterize APC subsets in adult peripheral blood (APB) and cord blood (CB). APB had a higher proportion of CD11cϩ dendritic cells (DC), whereas CB mainly contained CD123ϩ DC. APB was enriched in CD16ϩCD11cϩ DC subset, whereas CD34ϩCD11c-CD123lo cells were prominent in CB. Lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-␣ production was dampened in myeloid DC and monocytes from CB, whereas IL-1␣ production was not different. The reduction in TNF-␣ response did not appear to result from reduced surface detection of LPS, because CD14, toll-like receptor (TLR)-4 and TLR-2 levels were not reduced in CB APC compared with APB cells. Also, there was no correlation between TLR-2 or TLR-4 levels and TNF-␣ production in myeloid DC and monocytes. CB monocytes had lower surface HLA-DR immediately ex vivo. Both APB and CB monocytes upregulated HLA-DR after incubation, but an additional LPS-induced increase in HLA-DR was suggested only in APB monocytes. APB monocytes also showed a greater LPS-induced increase in CD40 expression. Together, our data show significant, selective differences in circulating APC between neonates and adults.
Intracellular cytokine production by fetal and adult monocytes
Journal of Pediatric Surgery, 2001
Background/Purpose: In light of the neonate's increased susceptibility to systemic infection, the authors hypothesized that adult and fetal monocytes have different cytokine expression profiles in response to lipopolysaccharide (LPS), and interleukin (IL)-11, a counter-inflammatory cytokine.