One of the major objectives of vaccine development is the establishment of immunization protocols that permit the selective induction of either Th1 or Th2 type immunity, as differentially required for the immune system to successfully overcome different infectious agents. For example, Th1 immunity is though to be required for controlling Leishmania major infection, while a Th2 response to this agent has pathological effects. The reverse might also be true, e.g. in the case of Helicobacter pylori infection. Recently the investigator has shown that immunization with a prototypic antigen, hen egg white lysozyme (HEL) injected in complete Freunds adjuvant (CFA), induces an immune response that is essentially pure Th1, while injection of HEL in incomplete Freunds adjuvant (IFA) results in an apparently pure Th2 response to HEL. Can adjuvants be used selectively to engage the desired class of response as needed for vaccinations against different infectious agents? Moreover, do the rules for adjuvant guided immune responses established in young adult mice also apply for aged mice? Specific Aim 1 proposes to characterize more closely the cytokine profile and immunoglobulin isotype of the anti-HEL response induced in Th2 biased BALB/c and Th1 biased C57BL/6 mice following immunizations with CFA, IFA or aluminum hydroxide, the primary adjuvant used in humans.
Specific Aim 2 proposes to test whether Th1 or Th2 type immunity can be selectively induced against Leishmania antigens by use of different adjuvants (preliminary data suggest that indeed this may be the case). Finally, Specific Aim 3 will test whether the anti-Leishmania Th1 response induced by CFA immunization protects otherwise susceptible, Th2 biased mice from Leishmania major infection. In the reverse experiments, it will be tested whether induction of Th2 immunity to Leishmania antigens renders naturally resistant C57 BL/6 mice susceptible to this infection. These studies will compared the immune responses of young adult and aged mice.
|Denkinger, Claudia M; Denkinger, Michael D; Forsthuber, Thomas G (2007) Pertussis toxin-induced cytokine differentiation and clonal expansion of T cells is mediated predominantly via costimulation. Cell Immunol 246:46-54|