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)

We previously used peripheral newborn blood (NBB) as a possible in vivo experimental model for cord blood (CB) transplantation and showed that B10.D2 NBB cells successfully reconstituted adult (DBA/2 x B10.D2)F1 mice without causing graft-versus-host disease (GVHD), probably because of their phenotypic and functional immaturity. Here we investigated the influence of T-cell maturation occurring in NBB cells during the early postbirth period on the degree of engraftment, the incidence of GVHD, and the graft-versus-leukemia (GVL) potential. These parameters were compared in recipients grafted with bone marrow (BM) cells. We observed an increased percentage of CD4(+) mature T cells accompanied by the acquisition of proliferative responses to phytohemagglutinin (PHA) and to allogeneic cells of day-5 NBB cells. The capacity of day-2 NBB to engraft was moderately reduced and recipients developing GVHD were occasionally observed after the graft of day-5 NBB cells. No GVL effect was evidenced regardless of the time of postbirth blood collection. However, the GVL effect can be obtained by the delayed infusion of donor mature T cells to recipients grafted with day-0 NBB, without causing GVHD. In contrast, the same protocol applied to mice grafted with BM cells induced GVHD mortality of all recipients. Interleukin (IL)-10 but not IL-2 messenger RNA was expressed in NBB cells as opposed to BM cells. These findings suggest that, in terms of GVHD incidence, delayed infusion of mature T cells as post-transplant tumor immunotherapy would be more effective when applied after CB than after BM transplantation.
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PMID:Graft-versus-host disease and graft-versus-leukemia effect in mice grafted with peripheral newborn blood. 980 91

In the present study we have examined immunophenotypic characteristics ofT-acute lymphoblastic leukemia (T-ALL) cells in relation to the expression of enzyme dipeptidyl peptidase IV (DPP IV). Peripheral blood and bone marrow cells of T-ALL patients at diagnosis were estimated. Cell surface markers were detected by a standard immunofluorescence assay and FACStar flow cytometry using a broad panel of monoclonal antibodies to define T-cell immunophenotype. DPP IV activity was investigated in phenotypically defined T-lymphoblasts. Association between DPP IV expression and proliferation was monitored by the expression of CD71 and CD38, which could be considered as markers of activation and proliferation, and by the silver-staining of nucleolar organizer regions-related proteins (argyrophilic proteins). Lymphoblasts, divided according to the presence or absence of DPP IV activity revealed remarkable heterogeneity in the immunophenotypic features. The vast majority of DPP IV positive T-ALL cases expressed CD4, CD8, CD7, CD5, CD2 along with CD71 and CD38 antigens, but the cells were surface membrane CD3 antigen negative. The phenotype of DPP IV negative cases displayed membrane CD3 antigen and variable expression of CD4 and CD8. CD71 and CD38 were frequently negative. It appears, that DPP IV active cells form the population with immature phenotype, as evidenced by mCD3 antigen absence. Relation between DPP IV positive cells and proliferation activity of T-blasts was observed, given by the presence of CD71 and CD38 positivity and overexpression of argyrophilic proteins (AgNORs). In conclusion, our study indicates a close relationship between DPP IV activity and the features ofT-cell immaturity. Association among DPP IV, CD71, CD38 and AgNORs might reflect possible relationship between immature phenotype and proliferative ability of blast cells in T-ALL patients.
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PMID:Immunophenotypic characteristics of T-acute lymphoblastic leukemia cells in relation to DPP IV enzyme expression. 989 Jun 67

From the biobreeding-diabetic prone (BB-DP) rat, an animal model for endocrine autoimmunity, phenotype and function of splenic dendritic cells (DC) were studied. Furthermore, the suppressive effect of peritoneal macrophages (pMphi) from the BB-DP rat in the MLR was investigated. Lower numbers of splenic DC were isolated from BB-DP rats than from control Wistar rats. In the preautoimmune phase, DC of the BB-DP rat had a lower surface MHC class II expression (and in preliminary data, a lower CD80 expression), ingested more bacteria, and had a lower stimulatory potency in the syngeneic (syn)MLR as compared with control DC. During disease development, the MHC class II expression further decreased, and a low stimulatory activity became evident in the allogeneic (allo)MLR. With regard to the expansion of suppressor/regulatory T cells, a lower percentage of RT6+ T cells but higher percentages of CD45RClow T cells were induced by BB-DP DC in synMLR, but not in alloMLR. An increase in the CD4/CD8 T cell ratio was observed in both the syn- and alloMLR due to a relative weak expansion of CD8+ T cells with DC of the BB-DP rat. Resident pMphi isolated from BB-DP or Wistar rats were equally effective in suppressing the DC-driven synMLR. In conclusion, splenic DC from the BB-DP rat have a lower accessory cell function already at young age, before the development of disease, and expanded different subsets of effector/suppressor T cells in vitro as compared with those from Wistar rats. The dysfunction of DC from BB-DP rats is likely to be caused by their relative immaturity as indicated by their low class II and costimulatory molecule expression and relatively high phagocytic activity.
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PMID:Signs of immaturity of splenic dendritic cells from the autoimmune prone biobreeding rat: consequences for the in vitro expansion of regulator and effector T cells. 997 44

It has been observed high risk of infections in neonates as a result from lymphocytes immaturity. It is connected to phenotype differences of lymphocytes between neonates and adults. This high susceptibility to infections is especially high in premature neonates. With the use of flow cytometry we have evaluated the phenotype of cord blood lymphocytes in premature neonates. In comparison to results of healthy newborns we have observed significant decrease in CD7+, CD3+, CD4+, CD25+, CD57+ lymphocytes an increase in total number of CD8+ cells as well as alteration in CD4/CD8 ratio. Our results suggest deeply damage of cellular immunity in preterm infants.
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PMID:[The phenotype characteristics of cord blood lymphocytes in premature neonates]. 1076 3

Because it is difficult to assess prenatally induced functional deficits of the human immune system, we developed an ex vivo method for differentiation and maturation of peripheral lymphocytes of newborn, preferentially using umbilical cord blood. Many lymphocyte subsets of newborn infants are "immature" with respect to defined surface receptors. An example of such an immaturity is the almost complete lack of "memory"-type helper T cells (also designated as helper-inducer cells), characterized by expressing the surface receptors: CD4(+)CD45R0(+)CD45RA(-)CD29(high). On the other hand, umbilical cord blood contains many "naive"-type helper T cells (often designated as suppressor-inducer cells), with the receptors: CD4(+)CD45R0(-)CD45RA(+)CD29(low). In this report, we demonstrate that the immature helper lymphocyte population of umbilical cord blood is capable of differentiating to mature cells following stimulation with pokeweed mitogen (PWM) and other stimulants ex vivo. The obtained receptor pattern is virtually indistinguishable from the one observed on the mature cells of adults. Such an extensive differentiation can only be achieved with cells of newborns. As intermediates during differentiation in culture, CD45R0(+)CD45RA(+) cells may be observed which are rather rare in vivo. Additionally, the appearance of several activation (CD25, CD69, HLA-DR) and adhesion (CD11a, CD11b, CD11c, CD18, CD49b, CD49d, CD54) receptors on CD4 cells were analyzed. With this model system evidence for the sequence of events during differentiation and maturation may be obtained. This ex vivo-model is capable of studying the capacity of lymphocytes for differentiation and activation processes barely accessible in vivo. It may also be expected to represent an interesting tool for measuring the capacity for maturation and differentiation in the blood of children of different ages under normal and pathological conditions ex vivo. In addition, substance-induced effects may be studied in vitro with this approach on immature cells from newborn, or infants during culturing. Teratogenesis Carcinog. Mutagen. 20:171-193, 2000.
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PMID:Assessing lymphocyte functions in neonates for revealing abnormal prenatal development of the immune system. 1091 Apr 69

Pneumococcal polysaccharide (PPS) antibody deficiency occurs in some children immunosuppressed following cardiac transplantation in early childhood. We studied lymphocyte subset populations in these children to identify patterns associated with antibody deficiency, particularly in CD21 + B cells. Lymphocyte surface markers CD3, CD4, CD8, CD19, and CD21 were measured on whole blood by FACS analysis in four patient groups: cardiac transplant patients who did and did not respond to PPS, nontransplanted cardiac patients, and normal controls. Absolute cell numbers were compared with age-related normal ranges. The proportion of children with values below the age-related 25th percentile in each group was compared. Normal controls had significantly more CD3+, CD8+, and CD19+ cells, even when age-related differences were accounted for. Control groups had significantly more CD19 cells than transplant patients and transplanted PPS responders and cardiac controls had more mature B cells (CD21+) than transplanted PPS nonresponders. PPS antibody deficiency following pediatric cardiac transplantation may be related to an immaturity in B cells due to immunosuppression commenced in early childhood.
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PMID:Lymphocyte subset populations in children with polysaccharide antibody deficiency following cardiac transplantation. 1132 Dec 37

Immune recovery after cord blood transplantation (CBT) is of concern owing to the low number of lymphocytes transferred with the graft and their immaturity. Risk factors influencing lymphocyte subset reconstitution related to disease, patient, donor and transplant were studied in 63 children (< 16 years), given either related (n = 14) or unrelated (n = 49) CBT for malignant (n = 33) or non-malignant diseases (n = 30). Only children with sustained myeloid engraftment were analysed. Absolute numbers of T (CD3(+), CD4(+), CD8(+)), B and natural killer (NK) cells were reported 2--3, 6, 9, 12 and 12--24 months after CBT. Median patient age was 4.0 years (0--15) and median follow-up was 23 months (1.7--61.0). Twenty-six patients received human leucocyte antigen (HLA)-matched CBT and 37 received HLA-mismatched CBT. The median number of nucleated cells (NCs) collected/recipient weight was 6.1 x 10(7)/kg. In this selected population, the estimate 2 year survival was 85%. Lymphocyte reconstitution (defined as the median time to reach the normal value of age-matched healthy children) was 3, 6 and 8 months for NK, B and CD8(+) cells, while it was 11.7 months for both CD3(+) and CD4(+) lymphocytes. In the multivariate analysis, factors favouring T-cell recovery were: related donor (P = 0.002); higher NCs/kg (P = 0.005) and recipient cytomegalovirus (CMV)-positive serology (P = 0.04). Presence of acute graft-versus-host disease (GVHD) delayed T-cell recovery (P = 0.04). To summarize, in children with sustained myeloid engraftment the concern that lymphocyte recovery after CBT could be delayed does not appear to be substantiated by our results.
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PMID:Factors affecting lymphocyte subset reconstitution after either related or unrelated cord blood transplantation in children -- a Eurocord analysis. 1147 43

The reduced incidence of graft-vs.-host disease following umbilical cord blood (CB) transplantation may be related to the functional immaturity of newborn T cells expressing mainly the naive CD45RA phenotype. Expansion of CD4(+) CD45RA(+) T cells using cytokines may benefit neonates and infants with human immunodeficiency virus (HIV) infection, as a preferential decline in CD4(+) CD45RA(+) cells has been noted as HIV disease progresses. The aim of the study was to investigate the effect of interleukin (IL)-15, a novel cytokine similar to IL-2 in biological activities, on CD45RA/RO expression and apoptosis in umbilical cord blood (CB) and adult peripheral blood (APB) mononuclear cells (MNCs). Prior to culture, CB MNCs contained a greater number of CD4(+) CD45RA(+) cells and fewer CD4(+) CD45RO(+) cells than did APB MNCs. When incubated with RPMI-1640 containing 10% fetal calf serum for 7 days, the percentage of CD45RA(+) cells within CD4(+) T cells (%CD45RA(+)/CD4(+)) significantly decreased compared to that of fresh CB MNCs. IL-15 exerted a dose-dependent increase of %CD45RA(+)/CD4(+) and a corresponding decrease of %CD45RO(+)/CD4(+) in CB MNCs, an effect not observed with APB MNCs treated with IL-15. The percentages of CD45RA(+) and CD45RO(+) expression within CD8(+) cells, however, were not influenced by IL-15, in either CB or APB MNCs. A greater number of CB MNCs underwent apoptosis than did APB MNCs after 7 days of culture in RPMI-1640 containing 10% fetal calf serum. IL-15 did not inhibit apoptosis but induced proliferation comparable to that achieved in APB MNCs. The ability of IL-15 to preferentially enhance the proliferation of CD4(+) CD45RA(+) cells in CB MNCs suggests a role for immunomodulative therapy in HIV-infected newborns and infants.
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PMID:Interleukin-15 enhances CD4(+) CD45RA(+) expression on umbilical cord blood mononuclear cells. 1155 15

To compare the expression of CD antigens on immune cells from umbilical cord blood (UCB) and bone marrow (BM) and analyze its clinical significance, the phenotypes of lymphoid cells and nucleated cells from 38 UCB and 10 BM samples were investigated by flow cytometry with double labeling monoclonal antibodies. The results showed that the immature lymphocytes (CD3(-) CD4(+)) were detected in UCB and higher than those in BM; cytotoxic T lymphocytes (CD3(+) CD16(+) CD56(+)) in UCB were significantly lower than those in BM. NK cells (CD3(-) CD16(+) CD56(+)) in UCB were higher than those in BM. The ratio of CD34(+) cells in nucleated cells of UCB was similar to that of BM, however, both the contents of myeloid (CD34(+) CD13(+) and CD34(+) HLA-DR(+)) and lymphoid (CD34(+) CD19(+)) progenitor cells in UCB were lower than those in BM. It is concluded that the immune cells in UCB possess immaturity, which might lead to mild GVHD after UCB transplantation. It is inferred from the higher ratio of NK cells in UCB, GVL will not decrease after UCB transplantation. The lower contents of myeloid and lymphoid progenitor cells in UCB probably accounted for the slow hematopoiesis and immune reconstitution following UCB transplantation.
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PMID:[A comparison between immunophenotypes of lymphoid cells from human umbilical cord blood and bone marrow and its significance]. 1251 12

Neonatal immaturity of the immune system is currently believed to generally limit the induction of immune responses to vaccine Ags and to skew them toward type 2 responses. We demonstrated here that Bordetella pertussis infection in very young infants (median, 2 mo old) as well as the first administration of whole-cell pertussis vaccine induces B. pertussis Ag-specific IFN-gamma secretion by the PBMC of these infants. IFN-gamma was secreted by both CD4(+) and CD8(+) T lymphocytes, and the levels of Ag-induced IFN-gamma secretion did not correlate with the age of the infants. Appearance of the specific Th-1 cell-mediated immunity was accompanied by a general shift of the cytokine secretion profile of these infants toward a stronger Th1 profile, as evidenced by the response to a polyclonal stimulation. We conclude that the immune system of 2-mo-old infants is developmentally mature enough to develop Th1 responses in vivo upon infection by B. pertussis or vaccination with whole-cell pertussis vaccines.
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PMID:Bordetella pertussis infection in 2-month-old infants promotes type 1 T cell responses. 1253 14


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