Rationale The role of antigen-specific T-cells in the mechanism of food allergy or maintenance of tolerance towards an innocuous antigen such as cow's milk is not yet fully understood. Methods To investigate the cow's milk-specific T-cell response of donors with various allergic backgrounds, T-cell clones were generated and their antigen-specific proliferation, cytokine production and activation status was determined. Results Cow's milk-specific T-cell clones of children with persistent cow's milk allergy are Th2 skewed compared to the T-cell clones of cow's milk-tolerant allergic and non-allergic controls. In the cow's milk-allergic patients the production of IL-4, IL-13 is significantly correlated with the expression of the activation marker CD25. T-cell clones of the allergic control subjects are characterized by a high production of IL-10, which is positively correlated with the production of IL-4 and IFN-γ and with the expression of CD25. T-cell clones derived from non-allergic control subjects do not produce high levels of cytokines nor express high levels of surface markers. As in the allergic controls, also in the non-allergic controls, IL-10 production was positively correlated with the expression of CD25. Conclusions The activation status of T-cells derived from persistent cow's milk-allergic donors is associated with the production of IL-4 and IL-13 whereas activated T-cell clones of cow's milk-tolerant control subjects are characterized by the production of IL-10 and to a lesser extent IFN-γ. These findings suggest that activated CD4 + T-cells (characterized by a high CD25 expression) may contribute to the tolerogenic immune response towards an antigen, such as cow's milk via the production of IL-10.