Cell-Mediated Response to Tetanus Toxoid

Cytokine Production and the T-helper Response
In a study by Robinson et al. (2004), mice were immunized intragastrically with Lactococcus lactis bacteria expressing tetanus toxoid fragment C (TTFC), and stimulated with latex particles coated with tetanus toxin (LP-TT).   It was found that the mesenteric lymph node cells of the immunized group secreted significantly lower levels of IFN-γ than the unvaccinated mice. 

To investigate the mucosal cellular response, CD4+ cells from the small intestine were isolated from each group and stained for intracellular cytokines.  Seven days after immunization, there were significantly higher amounts of IL-4, IL-5, IL-10, and IFN- γ present in the vaccinated group than in the control group.  These levels were still elevated at day 42, with a much higher proportion of IL-4 being produced (Figure 1).  It appears that a mixed Th1/Th­2 response was elicited, with a slight bias towards the Th2 response.

Figure 1. Percentages of cytokine-positive events in CD4+ mucosal cells, 7 and 42 days post-vaccination.  Closed bars = vaccination with TTFC plasmid; striped bars = vaccination with plasmid not containing TTFC; open bars = no vaccination (Robinson et al., 2004).

In an additional experiment by Robinson et al. (2004), mice were immunized intraperitoneally with either TT-expressing L. lactis or a vaccine consisting of TT and Freund’s complete adjuvant (TT-FCA).  It was found that splenocytes from the TT-plasmid group produced significantly higher levels of IL-4 than the control group (suggesting a Th2 response), but the group vaccinated with TT-FCA produced significantly higher levels of IFN-γ (suggesting a Th1 response). 

Can Adjuvants Polarize the T-helper Response?
A study by Comoy et al. (1997) found that mice immunized with TTFC in alum adjuvant produced significantly more IL-4 and less IFN-γ than mice immunized with TTFC and Freund’s complete adjuvant.  His results indicate that different Th­ responses are induced when using vaccinations that contain varying adjuvants; this notion has important implications for future vaccine design, which could eventually allow for the promotion of a specific type of T-helper response.



This web page was produced as an assignment for an undergraduate course at
Davidson College.

Contact: cahermes@davidson.edu