Linked Life Data

17162206

Source:http://linkedlifedata.com/resource/pubmed/id/17162206

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2006-12-12
pubmed:abstractText
T-cell homeostasis is regulated by several molecules; among these, interleukin (IL)-7 plays an essential role in the survival and homeostatic proliferation of peripheral naive T cells. In a previous study, we investigated whether human mesenchymal stromal cells (MSCs) could be engineered with the IL-7 gene to produce functional level of this cytokine. In the present study, we analyzed the impact of different quantities of IL-7 produced by MSCs on the survival and proliferation of a negative immunoselected naive (CD3(+)/CD45RA(+)) T-cell population. Co-cultivation of peripheral naive T cells with MSCs producing low (16 pg/mL) or high (1000 pg/mL) IL-7 levels or in the presence of exogenous IL-7 (0.01 ng/mL and 100 ng/mL) maintained the CD3(+)/CD45RA(+) naive T-cell phenotype. Chemokine receptor CCR7(+) expression was also maintained among this T-cell population. Naive T-cell molecular characteristics were maintained as assessed by the Vbeta spectratyping complexity score, which showed the maintenance of a broad T-cell repertoire. No Th1 or Th2 differentiation was observed, as assessed by interferon-gamma or IL-4 accumulation. In contrast, only MSCs producing high amounts of IL-7 caused increased activation (CD25 31.2% +/- 12% vs 10% +/- 3.5%; P < .05), proliferation (CD71 17.8+/-7% vs 9.3%+/-3, P < .05), apoptosis (assessed by annexin V: 18.6% +/- 5% vs 14.9% +/- 2.6%; P > .05), and the phase S cell cycle (15% vs 6.9%, P > .05). Exogenous IL-7 exhibited no significant effect. In conclusion, we demonstrated that IL-7 produced by MSCs has a dose-independent effect on naive T-cell survival while exerting a dose-dependent effect on activation/proliferation. Due to the continuous production of IL-7 by engineered cells, our system is more efficacious than exogenous IL-7.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1083-8791
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1250-60
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:17162206-Antigens, CD, pubmed-meshheading:17162206-Apoptosis, pubmed-meshheading:17162206-Cells, Cultured, pubmed-meshheading:17162206-Coculture Techniques, pubmed-meshheading:17162206-Dose-Response Relationship, Drug, pubmed-meshheading:17162206-Gene Rearrangement, beta-Chain T-Cell Antigen Receptor, pubmed-meshheading:17162206-Genetic Engineering, pubmed-meshheading:17162206-Genetic Vectors, pubmed-meshheading:17162206-Humans, pubmed-meshheading:17162206-Immunophenotyping, pubmed-meshheading:17162206-Interleukin-7, pubmed-meshheading:17162206-Mesenchymal Stem Cell Transplantation, pubmed-meshheading:17162206-Mesenchymal Stem Cells, pubmed-meshheading:17162206-Receptors, CCR7, pubmed-meshheading:17162206-Receptors, Chemokine, pubmed-meshheading:17162206-Recombinant Fusion Proteins, pubmed-meshheading:17162206-Retroviridae, pubmed-meshheading:17162206-S Phase, pubmed-meshheading:17162206-T-Lymphocyte Subsets, pubmed-meshheading:17162206-Transduction, Genetic
pubmed:year
2006
pubmed:articleTitle
Interleukin-7-engineered mesenchymal cells: in vitro effects on naive T-cell population.
pubmed:affiliation
Hematology and Clinical Immunology Section, Department of Clinical and Experimental Medicine, Perugia University, Perugia, Italy.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't