TRYPANOSOMA-CRUZI - PROTECTIVE IMMUNITY IN MICE IMMUNIZED WITH PARAFLAGELLAR ROD PROTEINS IS ASSOCIATED WITH A T-HELPER TYPE-1 RESPONSE

We have examined the ability of mice to survive a lethal challenge wit h the parasitic hemoflagellate, Trypanosoma cruzi, following immunizat ion with paraflagellar rod proteins (PAR) 1 and 2 either alone or in c ombination with the following adjuvants: Freund's, alum, QS-21, Ribi-7 00, or IL-12. PAR administered subcutaneously (sc) in combination with Freund's or alum provided significant protection, 100 and 83%, respec tively, against a T. cruzi challenge. In contrast, PAR in combination with QS-21, Ribi-700, IL-12, or Freund's administered intraperitoneall y (ip) or PAR alone provide no protection against a challenge. PAR-spe cific serum antibody titers and isotype profiles for several of the im munization regimens were determined, and no positive correlation could be seen between a protective immune response and either antibody tite r or the subclass of antibody induced. We also examined the ability of PAR to stimulate T cells from the spleen and lymph nodes of mice immu nized with PAR in combination with Freund's (sc), Freund's (ip), alum, or Ribi-700. Each of the adjuvants strongly enhanced the ability of e nriched T cells to proliferate in a PAR-specific fashion. suggesting n o obvious correlation between PAR-specific T cell activation and prote ction. However, examination of the cytokine profiles of the stimulated T cell groups showed that the protective groups differed from the non protective groups. While all four groups showed low levels of IL-10, t he Freund's (sc) and alum groups had higher levers of IFN-gamma and IL -2 than Freund's (ip) and Ribi-700 groups, and most strikingly, no IL- 4 could be detected in either the Freund's (sc) or the alum group, in contrast to significant levels of IL-4 in both the Freund's (ip) and t he Ribi-700 group. These findings indicate that protective immunity in mice immunized with PAR is associated with a Th1-type response. (C) 1 996 Academic Press, Inc.