Fetal Response to Antigenic Stimulus

Silverstein, Arthur M.; Uhr, Jonathan W.; Kraner, Keith L.; Lukes, Robert J.

doi:10.1084/jem.117.5.799

Cited by 219 publications

(45 citation statements)

References 20 publications

(26 reference statements)

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“…[27][28][29] Specific antibody responses to soluble antigens develop as early as 40 days gestation in the sheep with most responses mature by 120 days. 30,31 We expected that the immune system of the fetal sheep at 0.35 term gestation was sufficiently immature so that tolerance to adenovirus vectors, as has been shown for liver stem cells, 28 could be induced. However, we observed no evidence that the recombinant adenovirus administered was tolerated.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary inflammation associated with repeated, prenatal exposure to an E1, E3-deleted adenoviral vector in sheep

et al. 1999

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Fetal gene therapy may prove useful in treating diseases electively killed and 13 died in utero. The incidence of morthat manifest in the perinatal or early postnatal period.tality was higher than the р10% we have experienced with Adenoviruses effectively transfer gene expression to a varother fetal sheep studies and was not likely related to comiety of tissues but also stimulate inflammatory and immune plications arising from surgical or anesthetic procedures. responses. The purpose of this study was to test the Inflammatory and fibrotic responses were observed in the hypothesis that exposure of fetal sheep to a first generation lungs and may represent untoward long-term conseadenovirus vector encoding bacterial ␤-galactosidase, quences of in utero adenoviral gene therapy. Tolerance to Av1nBg, before the development of the immune system, is Av1nBg was not established, and repeated exposure to safe, minimizes inflammatory and immune responses and Av1nBg before birth was associated with significant patholinduces tolerance. A total of 22 fetal sheep was studied; of ogy and mortality. these, two were born with respiratory distress, seven were

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Section: Discussionmentioning

confidence: 99%

Pulmonary inflammation associated with repeated, prenatal exposure to an E1, E3-deleted adenoviral vector in sheep

et al. 1999

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“…However, and in contrast to laboratory mice, an adaptive immune system develops in many larger mammals (including human beings) at early stages of fetal development. [22][23][24][25][26][27] Thus, the appearance of immunological tolerance cannot be explained by a failure to generate adaptive immunity to foreign antigen, as was initially thought in mice.…”

Section: A Brief Historical Perspective On the Development Of Lymphocmentioning

confidence: 99%

At the crossroads between tolerance and aggression

Mold

McCune²

2011

Chimerism

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e do not grow absolutely, chronologically. We grow sometimes in one dimension, and not in another; unevenly. We grow partially. We are relative. We are mature in one realm, childish in another. The past, present and future mingle and pull us backward, forward, or fix us in the present. We are made up of layers, cells, constellations."-Anaïs Nin It has long been recognized that the developing immune system exhibits certain peculiarities when compared to the adult immune system. Nonetheless, many still regard the fetal immune system as simply being an immature version of the adult immune system. Here we discuss historical evidence as well as recent findings, which suggest that the human immune system may develop in distinct layers with specific functions at different stages of development. A Brief Historical Perspective on the Development of Lymphocytes in MammalsOver two decades ago, a model was proposed by Leonore and Leonard Herzenberg which suggested that the immune system in mammals did not arise in a linear fashion from immaturity to maturity, as is often believed, but rather in distinct layers which could perform unique functions at different stages of development.1 This model was supported by a series of observations, made first in avian species 2,3 and later in the mouse, 4-10 that revealed the existence of unique waves of lymphocyte production during fetal and neonatal development.

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“…This increased susceptibility is more pronounced after premature birth where it causes significant morbidity and mortality although species differences exist in the level of immune development at birth [9][10][11]. This has been partly ascribed to neonates having reduced complement factors, poor phagocytic capabilities [7] and an overall underdeveloped innate immune system and naïve adaptive immune system [12]. Indeed, within sheep the splenic rudiment, containing myeloid…”

Section: Introductionmentioning

confidence: 99%

Differential expression of pattern recognition receptors during the development of foetal sheep

Nalubamba

Gossner²,

Dalziel³

2008

Developmental & Comparative Immunology

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Pattern recognition receptors (PRRs) play a crucial role in the initiation of the adaptive immune response. Immunological competence of foetal lambs occurs progressively throughout gestation and in order to understand the role played by PRRs in foetal immunological competence we quantified transcript expression, in the skin and spleen, of the TLRs, key C-type lectins and CARD15 during the critical second trimester. These data show that lambs express the same spectrum of PRRs as the adult but that the level of expression for most is dependent on developmental age. Key findings include: TLR1 and TLR5 are expressed at high levels in the foetus but are low in the adult; in contrast TLR4, CD14 and CARD15 increase with age. In addition, TLR9 and TLR10 are expressed by the spleen and not the skin while CARD15 is low in the spleen and high in the skin Many thanks for the referees comments, they were very helpful. I am glad that they found the paper interesting, of value and worthy of publication, and that by-and-large, their concerns were relatively minor. In response to their specific comments:Referee #1: 1. The major concern is that the same data were published previously (reference 19). To some extent this is true -we have published sheep skin and spleen PRR transcript levels. However, the data in the two papers come from different animals. In this paper adult animals are specifically being compared with foetal animals -and the adult tissues come from yearling sheep of the same breed as the foetuses. Nevertheless, the data are similar. I think this is valid. Incidentally, reference 19 was in the original version -referring to both methods and adult expression levels. 2. I have improved our description of the source of tissues in the animals-adult tissue comes from exactly the same anatomical sites as foetal tissues. 3. I have further explained the statistics. Because there are so many variables, it would be easy to be utterly pedantic and compare every sample with every other sample. Although that has been done -and an examination of the error bars (standard deviations) in Figs 1 and 2 can give an assessment of significance -to explain it all in the text would be unacceptably tedious. I have focussed on interesting comparisonsespecially between foetal and adult samples. I hope this is satisfactory. If required I can give p values for every single comparison -which would be very boring. 4. I have added to the description of the spleen data. However, to generate a separate section comparing skin and spleen is, I think, unnecessary. I have made some comparisons between the two tissues but not in great detail as this is not the main thrust of the paper. Comparing skin with spleen in detail is not particularly informative or for that matter that valid. Mammalian neonates are known to have a reduced response to specific antigens and an increased susceptibility to bacterial infections and sepsis [7,8]. This increased susceptibility is more pronounced after premature birth where it causes significant morbidity and...

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Fetal Response to Antigenic Stimulus

Cited by 219 publications

References 20 publications

Pulmonary inflammation associated with repeated, prenatal exposure to an E1, E3-deleted adenoviral vector in sheep

Pulmonary inflammation associated with repeated, prenatal exposure to an E1, E3-deleted adenoviral vector in sheep

At the crossroads between tolerance and aggression

Differential expression of pattern recognition receptors during the development of foetal sheep

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