Intracellular cytokine production and cytokine receptor interaction of cord mononuclear cells: relevance to cord blood transplantation

Han, Ping; Hodge, Greg

doi:10.1046/j.1365-2141.1999.01696.x

Cited by 30 publications

(32 citation statements)

References 36 publications

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“…IFN-␥ production was also elicited, but at levels significantly lower than that of adults, perhaps reflecting the defects in IL-12R and T-bet expression noted above (42,43). Indeed, IFN-␥ levels in neonates were so low that we were unable to detect that cytokine by intracytoplasmic staining.…”

Section: Discussionmentioning

confidence: 78%

“…However, their ability to confer protection to newborn mice was unknown. Induction of protective Th1 responses is generally compromised in neonates, reflecting the reduced expression of IL-12R, STAT4, and T-bet by immature immune cells (42,43). Yet current results indicate that CpG ODN treatment can protect newborns from infection using Listeria as a model pathogen (19 -21).…”

Section: Discussionmentioning

confidence: 81%

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CpG Oligodeoxynucleotides Enhance Neonatal Resistance to Listeria Infection

Ito

Ishii

Gürsel

et al. 2005

The Journal of Immunology

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Infection by Listeria monocytogenes causes serious morbidity and mortality during the neonatal period. Previous studies established that immunostimulatory CpG oligodeoxynucleotides (ODN) can increased the resistance of adult mice to many infectious pathogens, including Listeria. This work examines the capacity of CpG ODN to stimulate a protective immune response in newborns. Results indicate that dendritic cells, macrophages, and B cells from 3-day-old mice respond to CpG stimulation by secreting IFN-γ, IL-12, and/or TNF-α. Spleen cells from CpG-treated neonates produce large amounts of cytokine and NO when exposed to bacteria in vitro. Newborns treated with CpG ODN are protected from lethal Listeria challenge and generate Ag-specific CD4 and CD8 T cells that afford long-term protection against subsequent infection. These results demonstrate that cellular elements of the neonatal immune system respond to stimulation by CpG ODN, thereby reducing host susceptibility to infectious pathogens.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 81%

CpG Oligodeoxynucleotides Enhance Neonatal Resistance to Listeria Infection

Ito

Ishii

Gürsel

et al. 2005

The Journal of Immunology

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“…Cells were stimulated for 4 h with PMA (25 ng/ml) and Ionomycin (1 Ìg/ml). Simultaneously, BFA (10 Ìg/ml) was added for disrupting intracellular Golgi-mediated transport, thus allowing cytokines to accumulate, yielding an enhanced cytokine signal that can be detected by flow cytometry [16].…”

Section: Intracellular Cytokine Analysismentioning

confidence: 99%

“…Under standard activation conditions, naïve neonatal T cells are functionally (although not intrinsically) deficient, both in vitro and in vivo [3], and are poor producers of pro-inflammatory cytokines [4,5]. It is established that pro-inflammatory cytokines play a significant role in the effector phase of graft-versus-host disease (GVHD), suggesting that GVHD is associated with a predominantly type 1 (Th1) response [6,7].…”

Section: Introductionmentioning

confidence: 99%

Age-Related Changes in Intracellular Th1/Th2 Cytokine Production, Immunoproliferative T Lymphocyte Response and Natural Killer Cell Activity in Newborns, Children and Adults

et al. 2003

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To evaluate the development of the neonatal immune system, we measured T lymphocyte response to Con A, intracellular IL-2, IL-4, IFN-γ and IL-10 production, and natural killer cell (NKC) activity in 12 very preterm, 12 preterm and 20 term neonates, 10 children and 10 adults. Immunoproliferation to Con A was significantly lower in cord blood than in children or adults. The percentage of CD4+ lymphocytes was significantly higher in newborns while CD8+ cells were higher at older ages, with a resulting gradual decline of the CD4+/CD8+ ratio. The percentage of IL-2-producing CD4+ and CD8+ cells was higher in all newborn groups than in children and adults, while the percentage of IL-4-producing cells was higher for CD8+ and lower for CD4+ cells in cord blood than in children and adults. Neonates had substantially lower percentages of CD4+ and CD8+ IFN-γ-producing cells. A significant negative correlation was observed between gestational age and IFN-γ-CD4+-, IL-2-CD8+-, and IL-10- CD4+-producing cells. In addition, a positive correlation was found between gestational age and IL-10-CD8+-producing cells. Percentages of CD4+/CD45RA+ cells were higher and CD4+/CD45RO+ percentages were lower in newborns than in children and adults. NKC activity in infants was significantly correlated with gestational age and significantly impaired compared to children and adults. On the whole, these results suggest a gradual development of immunity during gestation and show significant immaturity of cellular immune response at birth. The reduction of NKC activity, the lower proliferative response of T cells, the reduced cytotoxic response and a dysregulated cytokine production may contribute to the neonatal increased risk of infection and to the low incidence of graft-versus-host disease after cord blood transplantation.

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“…This is due in part to the lower number of mature T cells in the graft (functionally CB is a partially T-cell depleted graft) and to the nature of the CB T cells' responsiveness to allogenic stimulus. [16][17][18][19][20][21][22][23] The question posed to us was how to apply these observations to one's strategy for CB unit selection, especially when there are competing variables. In this review, we summarize the literature on selection strategy, comparing unrelated adult donor to CB searches, and provide our personal preferences on this issue.…”

Section: Introductionmentioning

confidence: 99%

Selection of cord blood unit(s) for transplantation

Wall

Chan

2008

Bone Marrow Transplant

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Selection of cord blood (CB) units for transplantation involves combining both cell dose and HLA matching as independent yet overlapping variables. Cell dose and cell yield at the time of transplant are critical given that the transplants are being performed with minimal cells for reliable engraftment. In transplants for malignant disorders, the greater allogenicity and lower relapse rate associated with the less well-matched units balance any benefit of better HLA matching on TRM. The only factor that has repeatedly been associated with improved outcome post CB transplant is cell dose. The CB inventories are rapidly increasing in size and the quality of CB units being banked (larger, better characterized) is improving. With this, some of our current limitations in CB availability will soon become moot. Explorations into CB expansion and multiple CB unit transplants are addressing the limited cell doses attainable with a single CB collection. [1][2][3][4] At this point, one must conclude that bigger is better when selecting CB units for transplantation.

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Intracellular cytokine production and cytokine receptor interaction of cord mononuclear cells: relevance to cord blood transplantation

Cited by 30 publications

References 36 publications

CpG Oligodeoxynucleotides Enhance Neonatal Resistance to Listeria Infection

CpG Oligodeoxynucleotides Enhance Neonatal Resistance to Listeria Infection

Age-Related Changes in Intracellular Th1/Th2 Cytokine Production, Immunoproliferative T Lymphocyte Response and Natural Killer Cell Activity in Newborns, Children and Adults

Selection of cord blood unit(s) for transplantation

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