Modulation of the human immune response by the non-toxic and non-pyrogenic adjuvant aluminium hydroxide: effect on antigen uptake and antigen presentation

Abstract

The regulatory effects of an adjuvant (aluminium hydroxide) on the early phase of the immune response have been investigated. Adsorbing a soluble antigen (tetanus toxoid) to aluminium hydroxide led to a significant increase (P less than 0.001) in antigen-induced T-cell proliferation (macrophage-T-cell interaction, MTI) making aluminium hydroxide-adsorbed antigens especially suitable to study immunoregulatory changes in the early phase of the immune response. First studies revealed that this increase was due to an enhancement of antigen uptake by the antigen-presenting cell. However, under conditions allowing for the uptake of comparable amounts of soluble (TTs) or aluminium hydroxide-absorbed (TTAL) antigen, T-cell proliferation in response to TTAL was still higher than in response to TTS. This difference was especially pronounced if suboptimal antigen concentrations were used and could be explained by differences in the TTS-versus TTAL-induced release of interleukin-1 (IL-1). Pulsing with TTAL led to a substantial increase in IL-1 release by monocytes (MO) which then subsequently augmented antigen-induced T-cell proliferation. This was further supported by addition of exogenous IL-1 to cultures of T cells and TTS-pulsed MOs, which also significantly increased the T cells' proliferative response. These findings demonstrate that in the early phase of the immune response, aluminium hydroxide exerts its regulatory effect at the level of the antigen-presenting and mediator-releasing accessory cell.