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| Status |
Public on Jun 25, 2014 |
| Title |
CD4+ T cells treated with TNFalpha blocking agents during activation. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Objective. TNFα is a potent pro-inflammatory cytokine playing a pivotal role in several autoimmune diseases. Neutralizing TNFα inhibits T cell proliferation and IFNγ production, and enhances suppressive capacity of regulatory T cells (Treg). Little is known about the mechanism of TNFα blocking agents on naïve T cell differentiation. Methods. Naïve CD4+ T cells were activated by dendritic cells (DC) in presence or absence of anti-TNFα agents. T cell polarization and activation was assessed during T cell differentiation. In addition, whole genome gene expression analysis was performed on anti-TNFα-treated T cells. Results. Neutralizing TNFα during priming of naïve CD4+ T cells by DC favors development of IL-10+ T helper (Th) cells at the expense of IFNγ induction. TNFα inhibits IL-10 via TNFRII, which becomes expressed after naïve T cell activation. While initial CD4+ T cell activation was not affected, neutralization of TNFα negatively affected later stages of T cell priming by counteracting full T cell activation and survival. Whole genome gene expression analysis revealed a regulatory gene profile of anti-TNFα-treated T cells. Indeed, neutralizing TNFα during naïve T cell priming enhanced the suppressive function of anti-TNFα-treated T cells. Conclusion. Inhibition of TNFα–TNFRII interaction affects late stage effector T cell development and shifts the balance of Th cell differentiation towards IL-10 expressing regulatory T cells, which may be one of the beneficial mechanisms in TNFα blocking therapies.
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| Overall design |
Naïve CD4+ T cells were CFSE labeled and co-cultured for 13 days with allogeneic dendritic cells in the presence or absence of anti-TNFα agents. After 13 days, the CFSElow T cells were FACS sorted. Samples were generated from three independent donors.
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| Contributor(s) |
Boks MA, Kager-Groenland JR, van Ham M, ten Brinke A |
| Citation(s) |
24568737 |
| Submission date |
Dec 08, 2012 |
| Last update date |
Aug 13, 2018 |
| Contact name |
Martine A. Boks |
| E-mail(s) |
m.boks@vumc.nl
|
| Organization name |
Sanquin Blood Supply
|
| Department |
Immunopathology
|
| Street address |
Plesmanlaan 125
|
| City |
Amsterdam |
| ZIP/Postal code |
1066 CX |
| Country |
Netherlands |
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| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA183430 |
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