Delineation of the functional capacity of human neonatal lymphocytes.

Splawski, Judy B.; Jelinek, Diane F.; Lipsky, Peter E.

doi:10.1172/jci115029

Cited by 101 publications

(52 citation statements)

References 50 publications

(27 reference statements)

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“…Taken together, these data suggest that an impaired induction of hBD2 as part of an immature intestinal innate immune defense may play an important role particularly in NEC as ELBW infants with an increase in fecal hBD2 concentrations showed a much more moderate course of the disease. This hypothesis is in line with several reports demonstrating an impaired innate and adaptive immune response in ELBW infants (1,2,20). As hBD2 has been shown to be at least partly regulated by TLR4 and MD2 signaling (10,21), we investigated expression levels of these receptor molecules during and 14 wk after NEC in the two surviving patients.…”

Section: Articles Hbd2 Expression In Elbw Infants With Necsupporting

confidence: 80%

Human β-defensin 2 expression in ELBW infants with severe necrotizing enterocolitis

et al. 2012

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Section: Articles Hbd2 Expression In Elbw Infants With Necsupporting

confidence: 80%

Human β-defensin 2 expression in ELBW infants with severe necrotizing enterocolitis

et al. 2012

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“…5) and B lymphoblastoid (data not shown) cell lines transfected with CD1c induced DN T cells to produce cytokines, neonatal B cells did not stimulate detectable levels of cytokines from DN T cells, perhaps due to a reduced level of costimulation. Previous studies have shown that neonatal B cells produce IgM but only low levels of IgG in response to agonistic signals that induce adult B cells (29) (Fig. 7A).…”

Section: Cd1c-directly Reactive T Cells Of Sle Patients Induce Igg Absmentioning

confidence: 80%

Human Double-Negative T Cells in Systemic Lupus Erythematosus Provide Help for IgG and Are Restricted by CD1c

Sieling¹,

Porcelli

Duong³

et al. 2000

The Journal of Immunology

115

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To understand the mechanism of T cell help for IgG production in systemic lupus erythematosus (SLE) we investigated the response of CD4- and CD8-negative (double-negative (DN)) T cells because 1) DN T cells are present at unusually high frequency in patients with SLE and can induce pathogenic autoantibodies; 2) the DN T cell repertoire includes cells restricted by CD1 Ag-presenting molecules; and 3) CD1c is expressed on a population of circulating B cells. We derived DN T cell lines from SLE patients and healthy individuals. In the presence of CD1+ APCs, DN T cell lines from SLE patients produced both IL-4 and IFN-γ, whereas DN T cells from healthy donors produced IFN-γ, but no IL-4. In general, cells from patients with highly active disease produced high levels of IFN-γ; cells from those with little activity produced high IL-4. Coculture of CD1c-directly reactive T cells from healthy donors with CD1c+ B cells elicited IgM Abs, but little or no IgG. In contrast, CD1c-directly reactive T cells from SLE patients induced isotype switching, with a striking increase in IgG production. Neutralizing Abs to CD1c inhibited the ability of DN T cells to induce IgG production from CD1c+ B cells, further indicating that CD1c mediated the T and B cell interaction. IgG production was also inhibited by neutralizing Abs to IL-4, correlating with the cytokine pattern of DN T cells derived from these patients. The data suggest that CD1c-restricted T cells from SLE patients can provide help to CD1c+ B cells for IgG production and could therefore promote pathogenic autoantibody responses in SLE.

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“…In this study we analyze the development of the IgG repertoire in preterm and term neonates during a postconceptional age of 24 to 68 wk, i.e., during the time period when neonatal immunocompetence gradually increases from the "immunodeficiency of extreme prematurity" to the ability to produce Abs against various groups of Ags (23,24). By comparing preterm and term neonates at an identical postconceptional age but after different environmental exposures, we could discern changes that are triggered by preterm birth from changes that occur during physiologic intrauterine development.…”

Section: Discussionmentioning

confidence: 99%

“…1). In vitro, when appropriate T cell help and an appropriate cytokine milieu are artificially provided, cord blood B cells of preterm infants are able to undergo class switch more efficiently than they apparently do in vivo (23,42).…”

Section: Discussionmentioning

confidence: 99%

The Postnatal Maturation of the Immunoglobulin Heavy Chain IgG Repertoire in Human Preterm Neonates Is Slower than in Term Neonates

Zemlin

Hoersch

Zemlin

et al. 2007

The Journal of Immunology

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During the perinatal period the development of the IgH chain CDR3 (CDR-H3) repertoire of IgM transcripts is maturity-dependent and not influenced by premature exposure to Ag. To study whether maturity-dependent restrictions also predominate in the perinatal IgG repertoire we compared 1000 IgG transcripts from cord blood and venous blood of extremely preterm neonates (24–28 wk of gestation) and of term neonates from birth until early infancy with those of adults. We found the following. First, premature contact with the extrauterine environment induced the premature development of an IgG repertoire. However after preterm birth the diversification of the IgG repertoire was slower than that after term birth. Second, the IgG repertoire of preterm neonates retained immature characteristics such as short CDR-H3 regions and overrepresentation of DH7–27. Third, despite premature exposure to the extrauterine environment, somatic mutation frequency in IgG transcripts of preterm infants remained low until they reached a postconceptional age corresponding to the end of term gestation. Thereafter, somatic mutations accumulated with age at similar rates in preterm and term neonates and reached 30% of the adult level after 6 mo. In conclusion, class switch was inducible already at the beginning of the third trimester of gestation, but the developing IgG repertoire was characterized by similar restrictions as those of the developing IgM repertoire. Those B cells expressing more “mature” H chain sequences were not preferentially selected into the IgG repertoire. Therefore, the postnatal IgG repertoire of preterm infants until the expected date of delivery differs from the postnatal repertoire of term neonates.

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Delineation of the functional capacity of human neonatal lymphocytes.

Abstract: Neonatal T cell-B cell collaboration was investigated utilizing a system of T cell-dependent polyclonal B cell activation and Ig secretion. In (J. Clin. Invest. 1991. 87:545-553.)

Cited by 101 publications

References 50 publications

Human β-defensin 2 expression in ELBW infants with severe necrotizing enterocolitis

Human β-defensin 2 expression in ELBW infants with severe necrotizing enterocolitis

Human Double-Negative T Cells in Systemic Lupus Erythematosus Provide Help for IgG and Are Restricted by CD1c

The Postnatal Maturation of the Immunoglobulin Heavy Chain IgG Repertoire in Human Preterm Neonates Is Slower than in Term Neonates

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