Experimental and spontaneous autoimmune disease in animals can effectively be prevented and treated by application of pathogenic autoreactive T cells in an attenuated form. This approach has become known as T cell vaccination. T cell vaccination exploits specifically the ability of the immune system to regulate its autoreactive T cells by mechanisms of network control. The success of T cell vaccination in a variety of rodent animal models has raised hopes for its use as an effective and specific therapy in human autoimmune disease. The aim of this study was to induce an anti-T cell response by T cell vaccination in humans and primates as a pre-clinical study into the feasibility and toxicity of T cell vaccination. Using bulk cultures of T cells from the peripheral blood or an inflamed joint, it was possible to induce a T cell response specific for the injected vaccine and its activation state both in rhesus monkeys and in two patients with active rheumatoid arthritis. In one of the patients there was already a spontaneous T cell response against a mitogen driven T cell line from the peripheral blood, but not against a control T cell line specific for tetanus toxoid, suggesting that regulatory T cell networks are operative in patients with autoimmune disease. Significant clinical effects or side-effects were not observed. The results suggest that T cell vaccination in humans is feasible and non-toxic. It is likely to influence an already ongoing regulatory process. Conditions for making T cell vaccination an effective therapy need still to be worked out by further studies both in primates and in less complex human immune processes.