Anti-TNF antibodies such as adalimumab are widely used in the treatment of immune-mediated inflammatory diseases. We previously demonstrated that CD4+ T-cells from patients with inflammatory arthritis treated with anti-TNF biologics had increased proportions of IL-10 expressing cells. This effect was recapitulated in vitro by stimulating CD4+ T-cells from healthy donors in the presence of anti-TNF. Here we show that stimulation of CD4+ T-cells in the presence of anti-TNF resulted in decreased activation and maturation as shown by decreased frequencies of CD25+ and CD69+ cells, and lower CD45RO+ cell frequency. These phenotypic changes were coupled with reduced cell proliferation. Furthermore, analysis of previously generated gene expression datasets of anti-TNF-treated IL-17+ or IFNg+ CD4+ T-cells revealed changes in multiple pathways associated with cell proliferation and cell cycle. Kinetics experiments further revealed that anti-TNF treatment led to delayed, rather than impaired T-cell activation and maturation. We investigated whether anti-TNF treated CD4+ T-cells acquired an anergic or suppressive phenotype. Anti-TNF treated CD4+ T-cells displayed some hyporesponsiveness upon restimulation but did not differentially affect responder T-cell proliferation or monocyte phenotype, compared to control-treated cells. Anti-TNF treated cells however displayed a reduced ability to induce IL-6 and IL-8 production by synovial fibroblasts and to a lesser degree by monocytes, compared to control-treated cells. Collectively, our findings demonstrate that anti-TNF treatment can result in delayed activation, maturation and proliferation of CD4+ T-cells. Although these cells did not acquire a global suppressive phenotype, they exerted reduced pro-inflammatory effects on synovial fibroblasts and monocytes. Funded by Versus Arthritis (#21139).