TNF-blocking therapy is successfully used in the treatment of immune-mediated and inflammatory diseases. Although the inhibition of inflammatory pathways in target tissues by anti-TNF therapy has been clearly described, the impact of TNF-blockade on peripheral T cell responses in humans is still unclear. Here we studied T cell effector functions in psoriasis patients before and after treatment with anti-TNF by measuring a wide panel of cytokines as well as cell division upon in vitro stimulation. In parallel, the modulation of T cell cytokine gene expression was evaluated in psoriatic skin lesions. Results clearly evidenced that TNF-blockade increases T cell cytokine responses, mainly Th1 and Th17, in peripheral lymphocytes upon stimulation. Importantly, TNF-blockade also induced a potent enhancement of IL-10 expression by different subsets of circulating leukocytes that was found to correlate with the clinical outcome of the therapy. Despite the enhanced T cell cytokine responses in the peripheral circulation, in psoriatic skin lesions the overall effect of TNF-blockade was a diminished expression of Th1 and Th17 cytokine genes, paralleled by augmented expression of Il10. These evidences indicate a negative regulatory role of TNF on T cell activation and effector functions and enlighten a new role for TNF-blockade in the up-regulation of IL-10 that may participate to the shut down of the inflammatory reaction. Ongoing work (1): TNF-blockade enhances T cell response to TcR stimulation. Ongoing work (2): Modulation of cytokine gene expression by TNF-therapy in intestinal mucosa of patients with Inflammatory Bowel Disease

(2009). Effect of anti-TNF therapy on T cell activation and effector functions in patients with chronic inflammatory diseases. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2009).

Effect of anti-TNF therapy on T cell activation and effector functions in patients with chronic inflammatory diseases

RAELI, LORENZO
2009-11-26

Abstract

TNF-blocking therapy is successfully used in the treatment of immune-mediated and inflammatory diseases. Although the inhibition of inflammatory pathways in target tissues by anti-TNF therapy has been clearly described, the impact of TNF-blockade on peripheral T cell responses in humans is still unclear. Here we studied T cell effector functions in psoriasis patients before and after treatment with anti-TNF by measuring a wide panel of cytokines as well as cell division upon in vitro stimulation. In parallel, the modulation of T cell cytokine gene expression was evaluated in psoriatic skin lesions. Results clearly evidenced that TNF-blockade increases T cell cytokine responses, mainly Th1 and Th17, in peripheral lymphocytes upon stimulation. Importantly, TNF-blockade also induced a potent enhancement of IL-10 expression by different subsets of circulating leukocytes that was found to correlate with the clinical outcome of the therapy. Despite the enhanced T cell cytokine responses in the peripheral circulation, in psoriatic skin lesions the overall effect of TNF-blockade was a diminished expression of Th1 and Th17 cytokine genes, paralleled by augmented expression of Il10. These evidences indicate a negative regulatory role of TNF on T cell activation and effector functions and enlighten a new role for TNF-blockade in the up-regulation of IL-10 that may participate to the shut down of the inflammatory reaction. Ongoing work (1): TNF-blockade enhances T cell response to TcR stimulation. Ongoing work (2): Modulation of cytokine gene expression by TNF-therapy in intestinal mucosa of patients with Inflammatory Bowel Disease
REALI, EVA
anti-TNF; T-cell; cytokines; immune system; inflammatory diseases
MED/04 - PATOLOGIA GENERALE
English
Scuola di Dottorato in Medicina Traslazionale e Molecolare
MEDICINA TRASLAZIONALE E MOLECOLARE (DIMET) - 45R
22
2008/2009
(2009). Effect of anti-TNF therapy on T cell activation and effector functions in patients with chronic inflammatory diseases. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2009).
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/10634
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