Infliximab (IFX) is a chimeric mAb that can lead to the appearance of anti-drug Abs. Recent research has identified the presence of circulating IFX-specific T cells in treated patients. The aim of the study was to analyze the functional characteristics of IFX-specific T cells, in particular their capability to produce biologically active regulatory cytokines. Drug-stimulated PBMCs or coculture systems were used to detect memory T cells in treated patients. The cytokines produced by IFX-specific T cells, T cell lines, and T cell clones were evaluated at the mRNA and protein levels. Drug infusion induced an increase in IL-10 serum levels in vivo, whereas other cytokines were unchanged. IL-10 mRNA was higher in IFX-stimulated PBMCs from treated patients compared with untreated patients. When analyzed longitudinally, an early IL-10 mRNA expression was observed. HLA class II-restricted IL-10 production by drug-specific T cells from exposed patients was observed in different experimental settings, such as a coculture system, sorted CD154