This study assessed in detail the influence of four different human proteins on the activation of CD4+ and CD8+ T lymphocytes and on the formation of regulatory T cells. Human whole-blood samples were incubated with four different human proteins. The effects of these proteins on the downstream immune-system response, on the expression of ... extracellular activation markers on and intracellular cytokines in T lymphocytes, and on the number of regulatory T cells (T-reg cells) were investigated via flow cytometry. Incubation with beta-actin or glyceraldehyde 3-phosphate dehydrogenase (GAPDH), which are cytoplasmic proteins, increased the expression of both extra-cellular activation markers (CD69 and HLA-DR) and intracellular cytokines but did not significantly affect the number of T-reg cells. In contrast, incubation with human albumin or insulin, which are serum proteins, reduced both extracellular activation markers and intracellular cytokine expression and subsequently increased the number of T-reg cells. These findings may help to explain the etiological basis of autoimmune diseases.