Generalized toxicity of L-leucyl-leucine-methyl ester for lymphocyte functions

This study investigated the hypothesis that sensitivity to L-leucyl-leucine-methyl ester (Leu-leu-O-Me) can be used to identify a role for cytotoxic lymphocytes in alloreactivity. Treatment of donor lymphocytes with Leu-leu-O-Me profoundly inhibited their ability to induce three separate models of murine graft-versus-host reaction (GVHR). This was observed for all aspects of GVHR examined, including weight loss, splenomegaly and activation of natural killer (NK) cells. These effects were not influenced by whether specific cytotoxic T lymphocytes (CTL) were involved in individual models of GVHR. Leu-leu-O-Me not only eliminated NK and CTL activity in vitro, but had identical effects on the proliferation of T and B lymphocytes in response to a variety of mitogenic stimuli. Finally, Leu-leu-O-Me prevented immune lymphocytes from mediating both class I and class II major histocompatibility complex (MHC)-restricted delayed-type hypersensitivity (DTH) responses in vivo. It is concluded that Leu-leu-O-Me has non-specific toxicity for most lymphocyte function and that it cannot be used as a specific means of predicting the functional roles of CTL.