Evaluation of the immunotoxicity of antiretroviral drugs using an in vitro method for the induction and measurement of a specific antibody response in human peripheral blood lymphocytes

By Luzzati, A.L. - Giacomini, E. - Giordani, L.

We studied the effects of the antiretroviral drugs 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (DDC) on the induction of a specific primary antibody response to the antigen SRC and on Pokeweed mitogen-induced polyclonal immunoglobulin (Ig) production in cultures of normal human peripheral blood lymphocytes. The results presented here show that AZT and DDC inhibited both systems in a dose-dependent way. However, inhibition of the antigen-specific antibody response occurred at drug concentrations significantly lower than those effective on the mitogen-driven polyclonal response. This was particularly striking for DDC, which was approximately 100 times more powerful, on a molar basis, on the specific antibody response than on polyclonal Ig production. Thus, in vitro systems for the induction of antigen-specific antibody responses in human lymphocytes may be important, sensitive tools for preclinical studies of the immunotoxicity of antiretroviral drugs.