Reduced expression of NFAT-associated genes in UCB versus adult CD4+ T lymphocytes during primary stimulation

Kaminski, Beth; Kadereit, Suzanne; Miller, Robin E.; Leahy, Patrick; Stein, Kevin; Topa, David A.; Radivoyevitch, Tomas; Veigl, Martina L.; Laughlin, Mary J.

doi:10.1182/blood-2003-05-1732

Cited by 79 publications

(78 citation statements)

References 54 publications

(65 reference statements)

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“…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: 78%

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%

CpG Oligodeoxynucleotides Enhance Neonatal Resistance to Listeria Infection

Ito

Ishii

Gürsel

et al. 2005

The Journal of Immunology

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“…An additional caveat of our approach is that we measured responses by IFN-g secretion, which may be altered in cord blood cells. 37 Nevertheless, we detected CMV-specific CD8 1 T cells in the majority of patients as early as days 42 to 56 after UCBT, demonstrating that priming of T cells to CMV occurs before thymopoiesis contributes significantly to the T-cell repertoire. 24 Chimerism analysis of a subset of patients demonstrated definitively that the CMV-specific T cells were of UCB origin, removing a caveat of prior studies of CMV immune reconstitution.…”

Section: Discussionmentioning

confidence: 99%

Cytomegalovirus-specific T cells are primed early after cord blood transplant but fail to control virus in vivo

McGoldrick

Bleakley

Guerrero

et al. 2013

Blood

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“…132 Microarray analysis of UCB and adult CD4T cells showed profoundly different groups of genes were transcribed after activation, indicating that the T-cell response from UCB T cells are considerably different than T cells from adults. 133 The decreased effectiveness of UCB CD4 þ T cells, while delaying immune reconstitution of transplant recipients, likely contributes to the decrease in GVHD seen after UCB transplants. 134 Ex vivo expansion of HSC may introduce additional immune dysregulation after UCBT.…”

Section: Recent Preclinical/clinical Hsc Expansion Investigationsmentioning

confidence: 99%

Ex vivo expansion of umbilical cord blood stem cells for transplantation: growing knowledge from the hematopoietic niche

Hofmeister

Zhang

Knight

et al. 2006

Bone Marrow Transplant

200

172

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Umbilical cord blood transplantation (UCBT) in adults is limited by the small number of primitive hematopoietic stem cells (HSC) in each graft, resulting in delayed engraftment post transplant, and both short-and longterm infectious complications. Initial efforts to expand UCB progenitors ex vivo have resulted in expansion of mature rather than immature HSC, confounded by the inability to accurately and reliably measure long-term reconstituting cells. Ex vivo expansion of UCB HSC has failed to improve engraftment because of resulting defects that promote apoptosis, disrupt marrow homing and initiate cell cycling. Here we discuss the future of ex vivo expansion, which we suggest will include the isolation of immature hematopoietic progenitors on the basis of function rather than surface phenotype and will employ both cytokines and stroma to maintain and expand the stem cell niche. We suggest that ex vivo expansion could be enhanced by manipulating newly discovered signaling pathways (Notch, Wnt, bone morphogenetic protein 4 and Tie2/angiopoietin-1) and intracellular mediators (phosphatase and tensin homolog and glycogen synthase kinase-3) in a manner that promotes HSC expansion with less differentiation. Improved methods for ex vivo expansion will make UCBT available to more patients, decrease engraftment times and allow more rapid immune reconstitution post transplant.

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Reduced expression of NFAT-associated genes in UCB versus adult CD4+ T lymphocytes during primary stimulation

Cited by 79 publications

References 54 publications

CpG Oligodeoxynucleotides Enhance Neonatal Resistance to Listeria Infection

CpG Oligodeoxynucleotides Enhance Neonatal Resistance to Listeria Infection

Cytomegalovirus-specific T cells are primed early after cord blood transplant but fail to control virus in vivo

Ex vivo expansion of umbilical cord blood stem cells for transplantation: growing knowledge from the hematopoietic niche

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