Beryllium, an adjuvant that promotes gamma interferon production

Beryllium is associated with a human pulmonary granulomatosis characterized by an accumulation of CD4(+) T cells in the lungs and a heightened specifi c lymphocyte proliferative response to beryllium (Be) with gamma interferon (IFN-gamma) release (i.e., a T helper 1 [Th1] response). While an animal m odel of Be sensitization is not currently available, Be has exhibited adjuv ant effects In animals. The effects of Be on BALB/c mice immunized with sol uble leishmanial antigens (SLA) were investigated to determine if Be had ad juvant activity for IFN-gamma production, an indicator of the Th1 response. In this strain of Leishmania-susceptible BALB/c mice, a Th2 response is no rmally observed after in vivo SLA sensitization and in vitro restimulation with SLA. If interleukin-12 (IL-12) is given during in vivo sensitization w ith SLA, markedly increased IFN-gamma production and decreased IL-4 product ion are detected. We show here that when beryllium sulfate (BeSO4) was adde d during in vivo sensitization of BALB/c mice with SLA and IL-12, significa ntly increased IFN-gamma production and decreased IL-4 production from lymp h node and spleen cells were detected upon in vitro SLA restimulation, No s pecific responses were observed to Be alone. Lymph node and spleen cells fr om all mice proliferated strongly and comparably upon in vitro restimulatio n with SLA and with SLA plus Be; no differences were noted among groups of mice that received different immunization regimens. In vivo, when Be was ad ded to SLA and IL-12 for sensitization of BALB/c mice, more effective contr ol of Leishmania infection was achieved. This finding has implications for understanding not only the development of granulomatous reactions but also the potential for developing Be as a vaccine adjuvant.