In vivo induction of type 1 and 2 immune responses against protein antigens

Polarization of the immune response towards T(h)1 or T(h)2 profiles is under the control of several, not yet well known, mechanisms. The present study was undertaken to investigate whether immune responses generated against major protein antigens, of parasitic (Schistosoma mansoni) and bacterial (Clostridium tetani) origin, present characteristic T-h profiles. Mice were immunized with a single dose of S. mansoni 28 kDa glutathione-S-transferase (Sm28-GST) or tetanus toxin fragment c (TTc) in combination with different adjuvants, or Salmonella typhimurium expressing these antigens as a fusion protein. Antigen-specific IgG isotypes and cytokine mRNA expression in vivo, as well as cytokine secretion after in vitro antigen stimulation were studied. Immunizations with either protein in aluminum hydroxide induced a strong T(h)2-associated antibody (IgG1) and cytokine (IL-4) response. In contrast, the recombinant S. typhimurium, expressing the TTc/Sm28-GST fusion protein, induced a T(h)1-like response, associated with the production of IFN gamma- and IgG2a antibodies against both antigens. When complete Freund's adjuvant was used, a non-polarized profile was observed, characterized by expression of both IL-4 and IFN-gamma as well as strong specific IgG1 and IgG2a antibody responses. These results indicated that some protein antigens play a weak role in polarizing the immune response and that contrasting cytokine profiles could be induced against the same antigen, depending on the adjuvant employed.