The subsets of lymphocytes and cytokines regulating the site-specific immune response in experimental cysticercosis (Taenia crassiceps) are not known. This study investigated the cells present at the site of infection (PECs) using flow cytometry and measured the cytokines produced by these cells through 50 days of infection. The results showed an expansion of B220+CD5+, B220+CD5-, alpha beta TCR+CD4+ and CD8+ cells coincident with a transient increase in IL-10 production. After the initial increase, the percentage of B220+CD5- and helper T cells decreased with a concomitant decrease in IL-10 production. CD8+ T cells continued to increase throughout infection and gamma delta TCR+ cells increased after 10 days of infection. PECs demonstrated an increased IFN-gamma and IL-4 production throughout infection when stimulated with larval antigens. Because a Th2-type polarization has been shown for spleen cells from infected BALB/c mice, cytokine profiles of spleen cells and PECs in response to ConA and larval antigens were compared. ConA and antigen-specific stimulation of spleen cells from 50-day-infected mice produced increased amounts of IL-10 while PECs showed a decreased IL-10 production suggesting that anatomically distinct lymphoid populations produce different cytokines and promote different types of responses. Surprisingly, late in infection the levels of IL-4 and IFN-gamma in serum increased substantially (460-fold and 100-fold, respectively). The systemic immune response of BALB/c mice during experimental cysticercosis, therefore, is a mixed Th1/Th2-type response.
The immunological events that occur during the initial stages of experimental cysticercosis are not known. The studies presented here examined the cytokines produced by peritoneal exudate cells (PECs), splenocytes and mesenteric lymph node (MLN) cells during the first week of infection with larval Taenia crassiceps in BALB/cJ mice. Proliferation assays determined that the earliest time when antigen-specific responses could be measured was 5 days post-infection. Concanavalin A (ConA) stimulation of host cells elicited an initial burst of IL-4 production at 24 h of infection and ConA-stimulated Th2-type cytokine production is predominant by 7 days post-infection. Thus, there are responses at day 1 of infection that seem to promote a Th2-type response. Stimulation of MLN cells, splenocytes and PECs with larval antigens supported previous reports of mixed Th1/Th2-type cytokine production with increases in interleukin (IL)-4, IL-10 and interferon (IFN)-c. Ex vivo IFN-c production by PECs from infected mice was increased at 3, 5 and 7 days postinfection, whereas at these times reduced ex vivo IL-10 production was observed. This ex vivo IFN-c response preceded an increasing IL-10 production by PECs between 3 and 7 days post-infection in parasite-specific and ConA-induced proliferation assays. Thus, infection with larval T. crassiceps results in an initial response mediated by IFN-c that is quickly followed by an increase in IL-10 production and subsequent reduction in the amount of IFN-c being produced.
Protective immunity against larval Taenia crassiceps has been shown to rely on T cells; however, the roles of the specific subsets of T cells during infection are not known. To investigate a possible role for gamma delta T cells, this study investigated larval infection in delta-chain knock-out C57BL/6 (deltaKO) and wild-type C57BL/6 mice. It was found that deltaKO mice and C57BL/6 mice were equally susceptible to infection suggesting gamma delta T cells do not play a major role in protective immunity. Cytokine production by concanavalin A (ConA)-stimulated spleen cells from infected deltaKO mice and C57BL/6 mice were determined. All infected mice demonstrated an increased IL-10 production suggesting a Th1-inhibitory function. Cells from infected deltaKO mice and C57BL/6 mice did not show increases in IL-4 production. Heavily-infected C57BL/6 mice showed a decrease in IFN-gamma production compared to deltaKO mice. These observations suggest that an increase in IL-10 production best correlates with a non-protective immune response. To make comparisons between in vitro cytokine production and systemic immune responses, cytokine levels in serum were determined. C57BL/6 mice and deltaKO mice showed increases in serum levels of IL-4 and IFN-gamma at 52 days post-infection. The systemic immune response of these mice, therefore, is a mixed Th1/Th2-type response and gamma delta T cells are apparently not responsible for the systemic increases in these cytokines.
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