IL-6, IL-5 and IFNƒ× levels in Balb/c mice inmunized with tetanus toxoid as a component of DPTw and DT vaccines

LAVIGNE MV; DELUCHI S; CASTRO MS; PIUDO L; DELLA VALLE MC; ATZORI C; MATEO N; CALCAGNO ML; BRERO ML; MANGHI MA

Bethesda, USA

Simposio; 6th National Symposium, Basic aspects of vaccines; 2000

Tetanus toxoid (TT), as a component of DTPw (particulate Ag) and DT (soluble Ag) vaccines, was used as a model protein antigen in T cell proliferation studies as well as in IL-4, Il-6, IFNg production. Twelve days  after the last immunization, spleen cells from 5 Balb/c mice injected with 4 doses of each vaccine and PBS (control) were “in vitro” stimulated, with ConA (mitogen), TT, heat killed B.pertussis (Bp) and TT/Bp. When DTPw and DT primed cells were stimulated with TT or TT/Bp, they showed a proliferative response 13-fold and 7-fold higher than control, respectively. Only DTP primed cells proliferated when Bp was used as stimulus. IFNg production was elicited by TT, TT/Bp and Bp in DTPw but not in DT primed cells. When IL-4 production was measured after 72 h culture,  all DTPw and 3 DT primed cells were responders to TT/Bp. As IL-4 and IFNg productions by spleen cells are associated with Th2 and Th1 responses, these findings demonstrate that the physical characteristics of antigens (soluble or particulate) can determine in what manner APCs process them. We have previously demonstrated that vaccination with DTPw, when compared with DTPacel, produces a tetanus response with lower neutralizing activity and higher content of asymmetrical glycosylated IgG molecules (60%), phenomenon  which could be associated with an increase of IL-6 production. The present studies show that TT/Bp stimulus is able to induce the production of IL-6 in DT primed cells, while TT is not. This indicates that the physical characteristics of antigens could modulate the expression of IL-6. This same IL-6 production pattern was shown by DTPw primed cells, producing a five-fold greater IL-6 level than DT primed cells (p< 0.001), probably due to the presence of Bp primed T cells. The pattern of cytokines observed in both vaccines might be associated with the ability of Bp to  particulate TT or with some immunomodulating component of Bp.