T-helper type-1-dominated lymph node responses induced in C57BL/6 mice by optimally irradiated cercariae of Schistosoma mansoni are down-regulated after challenge infection.
Following a single percutaneous vaccination with optimally irradiated cercariae of Schistosoma mansoni, C57BL/6 mice mount a T-helper type-1 (Th1) lymphocyte-dominant immune response and are highly resistant to challenge infection. In this study, we show that, besides interferon-gamma (IFN-gamma), lymph node (LN) cells draining the site of vaccination produce significant amounts of interleukin (IL)-4 and IL-10 in culture with parasite antigen. After a challenge infection at the original site of vaccination, these LN cells did not generate an anamnestic Th1 response. Paradosically, IFN-gamma production and cell proliferation were profoundly down-regulated, whereas IL-4 production was enhanced and occurred earlier than in challenge control cultures. When challenge was applied to a site remote from vaccination, IFN-gamma down-regulation was less evident, but the IL-4 response was consistently enhanced. Neutralization of IL-10 in vitro restored IFN-gamma production by LN cells, whilst IL-4 levels were reduced. These data indicate that down-regulation of IFN-gamma is controlled by IL-10 and/or IL-4. Mice showing down-regulated Th1 responses in the LN after S. mansoni challenge infection did not have a reduced ability to eliminate challenge parasites, indicating that the post-vaccination Th1 response had already armed the lungs with effector T cells before administration of challenge parasites. The observed phenomena of down-regulated Th1 and enhanced Th2 responses may be of relevance to other systems involving multiple infections or vaccination/boosting. Repeated applications to percutaneous sites having common lymphatic drainage would be expected to favour Th2 responses. Alternatively, in order to induce Th1-dominant responses and avoid unwanted IL-4/IL-10 induction, the use of remote sites is indicated.
Pemberton
R M
RM
Department of Biology, University of York, UK.
Wilson
R A
RA
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D000947:Antigens, Helminth; D016207:Cytokines; D007376:Interleukin-2; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma