The generation of interferon-gamma-producing T lymphocytes in skin-draining lymph nodes, and their recruitment to the lungs, is associated with protective immunity to Schistosoma mansoni.
We have examined immunological responses in the skin-draining lymph nodes (SLN) and lungs of mice during the 3 weeks after percutaneous exposure to attenuated larvae of Schistosoma mansoni. Cercariae irradiated with 20 krads (V20) were highly protective and sustained an increased number of CD4+ T cells in the SLN. On secondary exposure to schistosome antigen in vitro, these cells were capable of proliferating and secreting high levels of interferon-gamma (IFN-gamma) and interleukin-3 (IL-3). However, in mice exposed to non-protective 80 krad-irradiated (V80) cercariae, secretion of these cytokines occurred early and only transiently. Significantly elevated numbers of CD4+ T lymphocytes were recoverable on Day 21 from the lungs of V20, but not V80 mice. These cells secreted high levels of IFN-gamma and IL-3 in vitro, but not IL-2 and IL-4. Mice immunized intravenously with attenuated lung-stage schistosomula were not protected, despite having an elevated pulmonary lymphocyte population. Moreover these cells failed to secrete IFN-gamma and IL-3. However, significant protection was achieved where exposure of mice to a combination of V80 cercariae and lung-stage schistosomula resulted in the recruitment of IFN-gamma secreting cells to the lungs. We conclude that the success of the irradiated vaccine depends not only on the generation of a population of antigen-specific T-helper cells in the SLN, but also recruitment of these cells to the lungs before challenge.
Mountford
A P
AP
Department of Biology, University of York, U.K.
Coulson
P S
PS
Pemberton
R M
RM
Smythies
L E
LE
Wilson
R A
RA
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis*; D008168:Lung / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology*; D008482:Mediastinum; D051379:Mice; D008810:Mice, Inbred C57BL; D012550:Schistosoma mansoni / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000517:prevention & control; D012867:Skin; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000947:Antigens, Helminth; D007371:Interferon-gamma