THE GENERATION OF INTERFERON-GAMMA-PRODUCING LYMPHOCYTES-T IN SKIN-DRAINING LYMPH-NODES, AND THEIR RECRUITMENT TO THE LUNGS, IS ASSOCIATED WITH PROTECTIVE IMMUNITY TO SCHISTOSOMA-MANSONI

TY - JOUR

T1 - THE GENERATION OF INTERFERON-GAMMA-PRODUCING LYMPHOCYTES-T IN SKIN-DRAINING LYMPH-NODES, AND THEIR RECRUITMENT TO THE LUNGS, IS ASSOCIATED WITH PROTECTIVE IMMUNITY TO SCHISTOSOMA-MANSONI

AU - Mountford, A P

AU - Coulson, P S

AU - Pemberton, R M

AU - Smythies, L E

AU - Wilson, R A

PY - 1992/2

Y1 - 1992/2

N2 - 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 population of antigen-specific T-helper cells in the SLN, but also recruitment of these cells to the lungs before challenge.

AB - 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 population of antigen-specific T-helper cells in the SLN, but also recruitment of these cells to the lungs before challenge.

KW - IRRADIATED CERCARIAE

KW - PHASE IMMUNITY

KW - VACCINATED MICE

KW - RESISTANCE

KW - INDUCTION

KW - RESPONSES

KW - CHALLENGE

KW - CELLS

KW - MIGRATION

KW - ANTIBODY

M3 - Article

VL - 75

SP - 250

EP - 256

JO - Immunology

JF - Immunology

SN - 0019-2805

IS - 2

ER -