Histamine protects T cells and natural killer cells against oxidative stress

Oxidative stress inflicted by monocytes/macrophages (MO) is recognized as a n important immunosuppressive mechanism in human neoplastic disease. We rep ort that two types of lymphocytes of relevance for protection against malig nant cells, T cells and natural killer (NK) cells, became anergic to the T cell and NK cell activator interleukin-2 (IL-2) after exposure to MO-derive d reactive oxygen metabolities and subsequently acquired features character istic of apoptosis, The MO-induced anergy and apoptosis in T cells and NK c ells were reversed by histamine, an inhibitor of reactive oxygen metabolite synthesis in MO. We propose that strategies to circumvent oxidative inhibi tion of lymphocytes may be of benefit in immunotherapy of neoplastic diseas e.