IMMUNOBIOLOGY Suppression of T-cell functions by human granulocyte arginase

Chronic inflammation is accompanied by impaired T-cell immunity. In the mouse, myeloid cell–associated arginase ac-counts for the suppression of immune reactivity in various models of tumor growth and chronic infections. Here we show that arginase I is liberated from human granulocytes, and very high activi-ties accumulate extracellularly during pu-rulent inflammatory reactions. Human granulocyte arginase induces a profound suppression of T-cell proliferation and cytokine synthesis. This T-cell phenotype is due to arginase-mediated depletion of arginine in the T-cell environment, which leads to CD3 chain down-regulation but does not alter T-cell viability. Our study therefore demonstrates that human granulocytes possess a previously unan-ticipated immunosuppressive effector function. Human granulocyte arginase is a promising pharmacologic target to re-verse unwanted immunosuppression