Antibodies recognizing infliximab (IFX) may develop in a proportion of treated patients, leading to loss of response or hypersensitivity reactions (HRs). T cell response to IFX has been poorly investigated. This paper was addressed to detect IFX-specific T cells in treated patients with inflammatory diseases developing, or not, anti-drug antibodies (ADA) and to correlate the presence of specific T cells with the clinical outcomes of the treatment. A co-culture system of IFX-loaded dendritic cells and purified autologous CD4 T cells was used to detect memory T cells in 32 ADA and 39 ADA IFX-treated patients and control groups. The cytokine profile of IFX-specific T cells was also studied in culture supernatants. IFX-specific cell proliferation was detected mainly in cells from ADA patients, irrespective of their different diseases. HR patients displayed higher T cell proliferation than non-responder and tolerant patients. A mixed [interferon (IFN)-γ, interleukin (IL)-13, IL-10] cytokine profile was shown in cells from ADA patients, while IL-10 was the most frequently detected cytokine in the supernatants of cultures from ADA- patients. Immunoglobulin (Ig)E ADA patients with previous HRs exhibited a more pronounced type 2 profile than IgE ADA patients. This work provides evidence that IFX-specific circulating T cells are detectable mainly in ADA patients with HRs, regardless of their disease. The IFX-induced cytokine pattern partially correlates with the ADA isotype.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5108070PMC
http://dx.doi.org/10.1111/cei.12858DOI Listing

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