Comparative phenotypic analysis of lymph node cells in mice after infection or vaccination with normal or ultraviolet‐attenuated cercariae of Schistosoma japonicum or S. mansoni

Abstract

Mice were infected with 200 untreated or vaccinated with 500 ultraviolet-attenuated cercariae of either Schistosoma japonicum or S. mansoni. For three weeks, cell numbers in axillary and mediastinal lymphnodes were counted and cell populations typed by cytofluorometry. In the axillary lymphnodes, numbers of B-cells and CD3+CD4+ T-cells but not CD3+CD8+ T-cells increased. Following vaccination with either species, parasite migration was apparently delayed in the skin and interrupted at the lungs, the lymphnodes gained weight, and cell numbers of axillary lymph nodes increased more than after infection. In mediastinal lymphnodes, only immunization with S. japonicum but not S. mansoni cercariae led to an increase of CD3+CD4+ T-cells. Following infection, both schistosome species induced higher CD3+CD4+, but not CD3+CD8+ T-cells in mediastinal nodes, and the peak was earlier with S. japonicum (about seven days after infection) than with S. mansoni (about 10 days). In analogy to T-cell observations by others using a gamma-attenuated cercarial vaccine in S. mansoni, the present results suggest that CD3+CD4+ cells also play a role in the ultraviolet-attenuated vaccine against S. japonicum.

Accelerated influx of dendritic cells into the lymph nodes draining skin sites exposed to attenuated cercariae of Schistosoma mansoni in guinea‐pigs

“…Except for the serial changes in the number of DC noted in the present study, the proportional changes in SLN lymphocytes of Inf and Vac guinea-pigs are in agreement with those reported in the mouse model of infection and vaccination with S. mansoni, in which marked proportional increases of B cells have been described (Constant et al 1990, Lü et al 1995. Furthermore, it has been shown that S. mansoni elicits an extensive germinal centre response in both infected and vaccinated guinea-pigs, although the histological changes were noted on week 4·5 after exposure (Roger & McLaren 1987).…”

“…The response elicited by attenuated parasites was restricted to the skin-draining lymph nodes (SLN), although it was stronger and more sustained than that induced by normal cercariae. These results were similar to those in mice using the same UV-attenuation (Lü et al 1995) or girradiation (Constant, Mountford & Wilson 1990). The level of resistance is reduced by excision of the SLN , and the cells playing a key role in this immunity, CD4 þ T cells (Kelly & Colley 1988, Vignali et al 1989, proliferate almost exclusively in these lymph nodes.…”

“…In addition to TNF-a, IL-1b, and GM-CSF, induction of MHC class II antigens in keratinocytes within a few days of exposure (Sato et al 1997) indicates local production of interferon g. Keratinocytes are capable of secreting all the above cytokines constitutively or inductively by a variety of nonspecific stimuli, modulating inflammatory and immunological processes (Barker et al 1991, Bos & Kapsenberg 1993, Nickoloff & Turka 1994. A similar scenario may be true also following penetration of the skin by attenuated S. mansoni, and the retention of irradiated parasites in the skin over a period of 10 days (Kamiya & McLaren 1987, Kumagai, Sato & Kamiya 1992, Lü et al 1995) may provide such stimuli. We speculate that accelerated recruitment of DC in response to antigen-nonspecific stimuli by keratinocytes may contribute synergetically with modulated or increased antigenexpression of irradiated parasites (Wales, Kusel & Jones 1992, Wales et al 1993) to optimal T cell responses in the SLN.…”

Immune Events Associated with High Level Protection against Schistosoma japonicum Infection in Pigs Immunized with UV-Attenuated Cercariae

“…Our results showed that after attenuated cercariae immunization, granzyme b , nk-lysin , ifnγ , il12p40 , il4 and il10 genes expression levels, related with CD8 + T and CD4 + T, were higher than that after normal cercaria infection. In mouse and pig models, the T cell and DC proliferation in sdLN induced by irradiated cercariae is stronger than that induced by normal cercariae, and RA vaccination preferentially induces the accumulation of IFN-γ in the sdLN of mice [39], [40], [41]. Fragile bodies and slow migration in the RA could release a great amount of parasite antigens, or prolong the exposure to the host immune system, which may in turn favor the priming of protective responses [7].…”

Ultraviolet-attenuated cercariae of Schistosoma japonicum fail to effectively induce a Th1 response in spite of up-regulating expression of cytotoxicity-related genes in C57BL/6 mice

“…These results were quite inconsistent with the studies on radiated S. mansoni cercariae. Lu et al [18] found that T cell proliferation in the sdLNs elicited by UV-attenuated S. mansoni cercariae was stronger and more sustained than that induced by NC. Several studies showed that vaccination with irradiated cercariae of S. mansoni , preferentially induced the accumulation of IFN-γ producing T cells in the skin and sdLNs of mice[19].…”