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Naive Human T-Cells become Non-Responsive towards Anti-TNFα (Infliximab) Treatment In vitro if Co-Stimulated through CD28.
- Source :
- Scandinavian Journal of Immunology; Dec2008, Vol. 68 Issue 6, p624-634, 11p, 1 Chart, 6 Graphs
- Publication Year :
- 2008
-
Abstract
- Tumour necrosis factor α (TNFα) inhibitors are widely used successfully as immunomodulatory agents in various autoimmune diseases. They primarily target the direct pro-inflammatory effect of TNFα. They have also been found to be critical for T-cell viability and activation. In this study we evaluated the effect of infliximab treatment under different in vitro stimulatory conditions of naive human cord blood T-cells and adult peripheral blood mononuclear cells (PBMC). PBMC and negatively selected cord blood naive human T-cells were stimulated with αCD3 with or without αCD28 co-stimulation. The role of in vitro infliximab treatment was evaluated in relation to transforming growth factor-β1 (TGF-β1) under the above different stimulatory conditions. Anti-TNFα treatment with infliximab significantly suppressed proliferation of adult and cord blood T-cells ( P < 0.013) during suboptimal stimulatory conditions. Infliximab prevented division of naive CD4<superscript>+</superscript> and CD8<superscript>+</superscript> T-cells and consequently also activation induced cell death, which was induced after three cell divisions. Interleukin (IL)-2 secretion was significantly decreased during infliximab treatment of suboptimally stimulated T-cells ( P < 0.05) while TGF-β1 levels were unchanged. Strikingly, the anti-proliferative effect of infliximab was overcome by the administration of anti-TGF-β1 or by the addition of exogenous IL-2. Interestingly, CD28 mediated co-stimulation restored the proliferative response in a dose–responsive manner during infliximab treatment. Finally, exogenous TNFα administration during suboptimal stimulation reduced the inhibitory effect of TGF-β1 upon proliferation ( P < 0.03). These results demonstrate that anti-TNFα treatment is primarily working upon T cells under low stimulatory conditions and probably through TGF-β1. [ABSTRACT FROM AUTHOR]
- Subjects :
- HTLV-I
TUMOR necrosis factors
IMMUNE system
IMMUNOLOGIC diseases
T cells
Subjects
Details
- Language :
- English
- ISSN :
- 03009475
- Volume :
- 68
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- Scandinavian Journal of Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 34975891
- Full Text :
- https://doi.org/10.1111/j.1365-3083.2008.02181.x