INDUCTION OF TH1 AND TH2 CD4(-CELL RESPONSES BY ORAL OR PARENTERAL IMMUNIZATION WITH ISCOMS() T)

We examined the ability of oral or parenteral immunization with immune stimulating complexes containing ovalbumin (ISCOMS-OVA) to prime T ce ll proliferative and cytokine responses. A single subcutaneous immuniz ation with ISCOMS-OVA primed potent antigen-specific proliferative res ponses in the draining popliteal lymph node, which were entirely depen dent on the presence of CD4(+) T cells. CD8(+) T cells did not prolife rate in vitro even in the presence of the appropriate peptide epitope and exogenous interleukin (IL)-2. Primed popliteal lymph node cells pr oduced IL-2, IL-5 and interferon (IFN)-gamma, but not IL-4 when restim ulated with OVA in vitro. Serum antigen-specific IgG1 and IgG2a antibo dy responses were also primed by subcutaneous immunization with ISCOMS -OVA, confirming the stimulation of both Th1 and Th2 cells in vivo. Sp leen cells from subcutaneously primed mice produced a similar pattern of cytokines, indicating that disseminated priming had occurred. Oral immunization with ISCOMS-OVA also primed local antigen-specific prolif erative responses in the mesenteric lymph node and primed an identical pattern of systemic cytokine responses in the spleen. The ability of ISCOMS to prime both Th1 and Th2 CD4(+) T cell responses may be centra l to their potent adjuvant activities and confirm the potential of ISC OMS as future oral vaccine vectors.