T cell responses in psoriasis patients undergoing TNF-blocking therapy Tumor Necrosis Factor alpha (TNF) is a pro-inflammatory cytokine and plays a key role in the pathologenesis of chronic inflammatory diseases. For this reason, TNF has become the target of choice for biological therapies based on anti-TNF monoclonal antibodies or soluble TNF receptors. These have been successfully applied to the treatment of several autoimmune and inflammatory diseases, including rheumatoid arthritis, Crohn’s disease and psoriasis (Choo-Kang et al., 2005).
In addition to its role in inflammatory processes, TNF-alpha plays a role in activation and survival of T lymphocytes (Kim et al. 2006; Gupta et al., 2005) and in the cross-talk between Natural Killer (NK) cells and dendritic cells (DC) (Piccioli et al. 2002).
The aim of our project is to study T cell responses in psoriasis patients undergoing therapy with TNF-blocking agents. In particular, we are investigating whether TNF-blockade modifies T cell effector functions such as Th1/Th2 cytokine production and antigen-specific responses from the qualitative or quantitative point of view.
Furthermore, we assessed effector function and frequency of two T cell subsets (i.e., Th17 and T-regulatory cells, Treg), which regulate cellular immune responses.
Finally, we evaluated, by real time PCR, the expression of genes that encode pro-inflammatory and anti-inflammatory molecules in peripheral blood lymphocytes and skin biopsies, during anti-TNF therapy.
The results will provide important information on the regulation of T cell-mediated immune responses and will improve the understanding of the immune mechanisms underlying the therapeutic effect of TNF blocking agents.
References
Choo-Kang BS et al. TNF-blocking therapies: an alternative mode of action? Trends Immunol. 2005 26(10):518-22.
Kim, E.Y., et al., TNF receptor type 2 (p75) functions as a costimulator for antigen-driven T cell responses in vivo. J Immunol, 2006. 176(2): p. 1026-35.
Gupta, S., R. Bi, and S. Gollapudi, Central memory and effector memory subsets of human CD4(+) and CD8(+) T cells display differential sensitivity to TNF-{alpha}-induced apoptosis. Ann N Y Acad Sci, 2005. 1050: p. 108-14.
Piccioli, D. et al. Contact-dependent stimulation and inhibition of dendritic cells by natural killer cells. J.Exp. Med. 2002. 195(3): 335-341.
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