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Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have developed an animal model for congenital syphilis. Treponema pallidum is injected intravenously into pregnant rabbits and fetuses are infected in utero. As a prelude to characterizing the immunologic consequences of fetal infection, it was necessary to expand on the baseline information about newborn rabbit immune capabilities. Studies were undertaken to determine splenic macrophage and T lymphocyte functions with emphasis on newer immunologic parameters. Newborns aged 2 weeks were compared to adults. Macrophage capabilities in newborn rabbits differed from those of their adult counterparts. These cells produced similar basal levels of interleukin 1 (IL-1) but failed to respond to the IL-1 stimulants of lipopolysaccharide (LPS) or T. pallidum. Macrophages also exhibited diminished levels of la expression and increased levels of prostaglandin E2 (PGE2) secretion. T lymphocyte functions were altered in newborn spleen preparations. Following concanavalin A (Con A) stimulation, interferon gamma production was half that of adults; in direct contrast, IL-2 production was twice that of adults. Con A-induced lymphocyte proliferation was markedly decreased in newborn preparations. This diminished response resulted from down-regulation rather than immaturity. When newborn splenic cells were stimulated with Con A in the presence of indomethacin, anti-transforming growth factor (anti-TGF), or exogenous IL-1/IL-2, better proliferation resulted. PGE2, which is well established as a down-regulator of newborn immune functions in human and mouse systems, also appears to play a role in suppressing newborn rabbit functions. TGF is a potent suppressor of a number of adult immunologic reactions. This is the first documentation of the potential role of this factor in down-regulating newborn immune capabilities. These findings provide a framework for future investigations of our congenital syphilis model.
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PMID:Macrophage and lymphocyte functions are down-regulated in newborn rabbits. 143 51

Mitogen-stimulated spleen cells from newborn mice do not synthesize mRNA for the 55-kDa interleukin-2 receptor (IL-2R). The kinetic of development after birth of ability to synthesize IL-2R correlated well with the functional immaturity of T cells, as was tested by responsiveness to T-cell mitogen concanavalin A (Con A). This functional immaturity of T cells was not due to the activity of neonatal suppressor cells (NSC) which inhibited immune responses induced by mitogens or antigens. The suppressor cells did not inhibit proliferation of spleen cells stimulated with IL-1 or IL-2, nor did they inhibited expression of genes for tumor necrosis factor (TNF)-beta, TNF-alpha, and IL-2R in stimulated cells from adult mice. The results thus show functional immaturity of T cells in newborn mice and selectivity of the immunosuppressive action of NSC, which allow for production and for functional activity of cytokines at a time when the specific immune system is not functional because of both immaturity and a selective activity of inhibitory cells.
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PMID:Immunological nonreactivity of newborn mice: immaturity of T cells and selective action of neonatal suppressor cells. 183 88

Neonatal B cells have been considered immature because of their impaired capacity to produce immunoglobulins in response to polyclonal activators in vitro. Here we demonstrate that cord blood mononuclear cells (MNC) produce normal levels of IgE in vitro when cultured in the presence of interleukin-4 (IL-4), indicating that the B cells are mature in their capacity to switch to IgE-producing cells. However, in contrast to adult peripheral blood T cells, cord blood T cells failed to produce detectable levels of IL-4 upon activation by phytohaemagglutinin (PHA) concanavalin A (Con A) or combinations of PHA and the phorbol ester TPA. Interferon-gamma (IFN-gamma) production by cord blood T cells following activation by Con A or PHA was also strongly reduced. However, high levels of IFN-gamma, significantly higher than those produced by adult T cells, were synthesized in response to combinations of PHA and TPA, indicating that IFN-gamma production by cord blood T cells is not intrinsically defective. In contrast, cord blood T cells produced levels of IL-2 that were significantly higher than those obtained by adult T cells tested in parallel. Collectively, our data indicate that the minimal levels of IgE production measured in cord blood (less than 1 U/ml) are not due to immaturity of the cord blood B cells, but may be associated with the failure of cord blood T cells to produce detectable levels of IL-4, which has been shown to be responsible for induction of IgE synthesis both in vitro and in vivo.
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PMID:Cord blood B cells are mature in their capacity to switch to IgE-producing cells in response to interleukin-4 in vitro. 211 17

We examined the nature of cytoplasmic signal transduction pathways in cord blood T cells by stimulating them with tumor promoter (TPA) and calcium ionophore (A23187). Costimulation of T cells with TPA and A23187 induced optimal proliferative responses on Day 2 in cord T cells but on Day 4 in adult T cells. The maximal responses observed in cord T cells were much less than those of adult T cells, whereas the Con A-induced proliferative responses of these cells showed no significant differences. The reduced responses of cord T cells were due to their lower efficiency in activating the cellular events in T cell activation and proliferation phase, because cord T cells have significantly less ability than adult T cells to express IL-2 receptor as well as HLA-DR and produce IL-2 molecules, thereby inducing proliferation. These data show immature characteristics of intracellular signal transduction pathways in cord T cells, which are directly related with the functional immaturity of cord T cells.
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PMID:Demonstration of functional immaturity of signal transduction pathways in human cord T cells. 251 Sep 37

Deficient responses by NK cells may contribute to the susceptibility of human newborns to severe HSV infections. Furthermore, HSV disseminates widely during neonatal infection and may also infect and interfere with the function of blood mononuclear cells (MNC). To determine whether the function of newborn NK cells would be affected by contact with HSV, and whether newborn NK cells might be permissive for HSV replication, newborn MNC were cultured with HSV in vitro for 3 days. Before culture, the intracellular calcium mobilization in newborn NK cells induced by mAb to CD2 and CD16 did not differ from that of adult NK cells. This result argues against immaturity of an early NK cell activation event in human newborns. After culture with HSV the Ca2+ flux response was unaffected by lysis of K562 targets by newborn NK cells and NK-dependent suppression of HSV replication in fibroblasts were preserved or increased. Incorporation of thymidine by NKH-1 cells following stimulation with PHA and IL-2 was not suppressed. NK cells recovered from these cultures did not contain infectious HSV and synthesis of HSV-specific proteins was not detected by immunoprecipitation although HSV genome was detected by DNA hybridization. Our results extend the in vitro model stimulation systems in which newborn NK cells respond positively to include triggering through the CD2 Ag, cross-linking of cell surface CD 16 Ag and response to a pathogen, HSV.
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PMID:Human newborn natural killer cell responses to activation by monoclonal antibodies. Effect of culture with herpes simplex virus. 253 66

A study was carried out on cord blood T cell activation via the CD2-mediated pathway. Despite similar percentages of circulating CD3+ and CD2+ cells in adult and cord blood, the proliferation of cord PBMC to the anti-CD3 mAb and cord T cells to anti-CD2 mAb were defective. The T cell CD3-surface structure was normally able to control CD2-mediated activation, as its modulation by a non-mitogenic anti-CD3 mAb blocked cord PBMC proliferation induced by anti-CD2 mAb. CD2-stimulated cord T cells did not proliferate and did not produce a significant amount of IL-2 in culture, although they expressed the IL-2R. This observation was confirmed by the optimal proliferation of CD2-induced cord T cells when rIL-2 was added. Despite the alternative T cell activation pathway is monocyte-independent in adults, the defective cord T cell activation via the CD2 molecule could also be bypassed by the addition of PMA, small amounts of either autologous or allogeneic adult and cord AC or simply rIL-1 alone. Our findings provide evidence for an intrinsic functional defect in cord CD2-mediated T cell activation, which is linked to an impaired increase of free cytoplasmic calcium, as confirmed by the effectiveness of calcium ionophore A23187 in restoring a good CD2-induced cord T cell proliferation and by measurement of cellular calcium uptake after activation via the CD2 molecule. The characteristics of cord T cells revealed by this study recall the thymocyte functional pattern and may represent functional expression of the previously described phenotypic immaturity of cord T cells.
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PMID:Activation of cord T lymphocytes. I. Evidence for a defective T cell mitogenesis induced through the CD2 molecule. 256 56

Lymphocytes from patients after bone marrow transplantation (BMT) are in most cases predominantly of the Leu-2+ (cytotoxic/suppressor) phenotypes and are almost unresponsive to mitogens. In contrast, normal Leu-3+-depleted, Leu-2+-enriched lymphocyte suspensions retain approximately 50% of the mitogenic response compared with that of unseparated cells. To investigate whether this discrepancy was due to active suppression, we selected nine BMT patients from whom sufficient numbers of cells were available and whose lymphocyte phenotypes were predominantly Leu-2+ after BMT. These post-BMT lymphocytes were tested for functional suppressor activities against donor and recipient pre-BMT lymphocytes in the lymphocyte transformation test. None of these post-BMT cells suppressed the response of donor or pre-BMT cells to phytohaemagglutinin A or concanavalin A. In contrast, the response of donor cells in mixed lymphocyte cultures to HLA-DR-different third-party cells was suppressed by highly X-irradiated post-BMT cells by approximately 40%. Addition of T-cell growth factor (= interleukin 2 (IL-2)) or X-irradiated donor cells to post-BMT lymphocytes partially restored the mitogenic response. These findings indicate that the early post-BMT cells lack production of IL-2 but are capable of responding to IL-2 and that the almost extinct mitogen response of these cells is due to immaturity rather than active suppression. The suppression of the allogeneic but not the mitogenic response might be explained by differences in the modes of activation; for example, the allogeneic response must involve the T-cell receptor, while the mitogenic response may not.
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PMID:The immunodeficiency of bone marrow-transplanted patients. The effect of patient lymphocytes on the response of donor lymphocytes to mitogens and allogeneic cells. 293 97

HIV infection induces both immune deficiency and immune stimulation. Central to the pathology of HIV infection is reduction in the numbers and function of CD4 T cells. Impaired functions include decreased proliferation, IL-2 receptor expression and production of lymphokines (IL-2 and gamma interferon (IFN]. HIV infection stimulates B cells and CD8 T cells. This is seen relatively soon after HIV infection. Increased activation and immaturity are seen in both these cell groups. In vitro studies confirm HIV stimulation of these cells. Studies have been conducted on patients with AIDS and opportunistic infection (OI) or Kaposi's sarcoma (KS), with AIDS-related complex (ARC) or with persistent generalized lymphadenopathy (PGL), as well as on asymptomatic HIV-seropositive and -seronegative homosexually active men. The latter group has been followed at 6-month intervals for the past 2-3 years. Those who seroconverted (became HIV-infected) were studied to investigate early changes following HIV infection. To delineate the immunopathology of infection with HIV, serial testing of seropositive individuals was carried out to determine the rate of CD4-T-cell reduction. Lowered CD4-T-cell number and percentage and CD4/CD8 ratio correlate with the occurrence of AIDS and with survival after AIDS-KS diagnosis. Seropositive individuals, however, differed markedly in the rate of CD4-T-cell reduction; in some, no reduction in CD4 cells occurred over a two-year period of observation. We propose that, in individuals in which CD4 levels have reached a plateau, effective host resistance to further CD4 cytoreduction has occurred.
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PMID:Immune pathogenesis of AIDS and related syndromes. 295 95

B lymphocyte differentiation into immunoglobulin secreting cells is a process depending on the presence of functionally mature B lymphocytes, monocytes and regulatory T lymphocytes. Cord blood B lymphocytes present in isolated cord blood mononuclear cell (MNC) preparations are normally unable to differentiate into immunoglobulin secreting plaque forming cells (PFC) when cultured in the presence of pokeweed mitogen (PWM) alone or killed Staphylococcus aureus Cowan 1 (SAC1) alone. However, each one of these activators induces PFC formation by B lymphocytes in adult MNC cultures. In the present study we show that these two activators can act synergistically to induce a significant in vitro PFC response in cord blood MNC's. The synergism of PWM and SAC1 exhibits a requirement for a specific sequence of addition in order to induce a positive response in neonatal cells. If both activators are not added simultaneously at the initiation of culture, only the initial addition of SAC1 followed by PWM will result in increased PFC production. The action of PWM and SAC1 on cord blood MNC can each be replaced by conditioned media. Supernatants from monocyte cultures containing soluble factors such as interleukin-1 (IL-1) can substitute for the activity of SAC1 while supernatants containing soluble T-cell factors (interleukin-2[IL-2], T cell replacing factor (TRF), B cell differentiation factor (BCDF), etc) can replace PWM in the cord blood MNC cultures. The results suggest that the synergistic effect of these two activators overcomes a partial immaturity or an excessive suppressor activity of human cord blood MNC.
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PMID:Cord blood B cell differentiation. Synergistic effect of pokeweed mitogen and Staphylococcus aureus on in vitro differentiation of B cells from human neonates. 637 19

IgG, IgA, and IgE production by newborn B cells is limited both in vivo and in vitro in various activation conditions, whereas IgM production is readily detectable. It has been suggested that the Ig heavy chain switch inability could be the consequence of T and B cell immaturity. As the interaction between CD40 (expressed on B cells) and its ligand CD40-L (expressed on activated T cells) triggers a key signal required for isotype switching, we studied the expression and function of these two components in normal fetuses, newborns, and infants, compared with adults. CD40-L expression was not inducible in 28 of 30 specimens of newborn cord-blood T cells following incubation with PMA and ionomycin, whereas activation markers such as CD69 were inducible. CD40-L expression was triggered by activation of T cells from infants > 3 wk of age. Surprisingly, T cells from 19- to 28-wk-old fetuses also expressed CD40-L following activation. CD40-L expression on newborn T lymphocytes was induced on T cell lines generated in the presence of PHA and maintained with IL-2 following further stimulation with PMA and ionomycin. CD40-L mRNA transcripts and intracytoplasmic protein expression following activation of newborn T cells were strongly decreased, leading to undetectable protein membrane detection. These results point to a possible transcriptional down-regulation of CD40-L expression by neonatal T lymphocytes. In addition, fetal and cord-blood B cells were poorly able to switch to IgG or IgA by stimulation with CD40 agonists (Ab or soluble CD40-L) in the presence of IL-4 or IL-10 as also detected with surface IgD+ adult B cells. Both phenomena could contribute to the neonatal Ig switch inability, although distinct underlying regulatory mechanisms are probably involved, as suggested by different in vivo time courses.
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PMID:Undetectable CD40 ligand expression on T cells and low B cell responses to CD40 binding agonists in human newborns. 753 Jul 39


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