HUMORAL AND CELLULAR-RESPONSES INDUCED BY INTRADERMALLY ADMINISTERED CYTOKINE AND CONVENTIONAL ADJUVANTS

Serum antibody responses to the model protein antigen avidin were monitored in sheep following intradermal injection of avidin formulated with a range of commercially available and experimental adjuvants, including muramyl dipeptide (MDP), aluminium hydroxide gel (alum), recombinant ovine interleukin-1 beta (rovlL-1 beta), rovlL-1 beta + alum, Quil A + alum or Emulsigen Plus. The highest antibody responses were recorded for animals immunised with avidin in rovIL-1 beta + alum, Quil A + alum or Emulsigen Plus, with moderate responses resulting from use of rovIL-1 beta or alum alone as adjuvants. Lower antibody responses to avidin were recorded when avidin was administered alone or with MDP. Delayed-type hypersensitivity (DTH) responses to avidin indicated that the most pronounced cellular response occurred in animals immunised with rovIL-1 beta + alum. Local cellular changes induced after primary and secondary intradermal injections indicated that distinct patterns of cellular recruitment were induced by the different adjuvants. Avidin with MDP resulted in an elevation of CD4+ T cells in the upper dermis while Emulsigen Plus induced an infiltration of large numbers of neutrophils throughout the dermis and reticular layers. CD4+, CD8+ and gamma delta+ T cells increased in number and were found evenly distributed throughout these regions. Alum-based adjuvants resulted in the development of distinct cellular accumulations comprising primarily CD4+ T cells and CD45R+ B cells arranged in distinct foci in the reticular layer. These cells were strongly class II positive as were the majority of macrophage like cells surrounding the foci. Staining for factor VIII related antigen indicated the presence of endothelial venules in the T and B cell foci and surrounding tissues.