TNF is essential for the cell-mediated protective immunity induced by the radiation-attenuated schistosome vaccine

M Street; P S Coulson; C Sadler; L J Warnock; D McLaughlin; H Bluethmann; R A Wilson

TNF is essential for the cell-mediated protective immunity induced by the radiation-attenuated schistosome vaccine

M Street, P S Coulson, C Sadler, L J Warnock, D McLaughlin, H Bluethmann, R A Wilson

Biology

Research output: Contribution to journal › Article › peer-review

Abstract

C57BL/6 mice exposed to the radiation-attenuated schistosome vaccine exhibit high levels of protective immunity. The cell-mediated pulmonary effector mechanism involves IFN-gamma-producing CD4(+) T cells in a focal response around challenge larvae. IFN-gamma can promote production of TNF and can synergize with this cytokine in its actions on responder cells, We have examined whether TNF plays a role in lung phase immunity to schistosomes using mice with a disrupted gene for TNFRI (TNFRI-/-). The most dramatic finding was that the schistosome vaccine elicited no protection whatsoever in these mice. However, this could not be attributed to a lack of responder cells, because more lymphocytes were lavaged from the airways of TNFRI-/- than wild-type mice. Furthermore, CD4(+) T cells were equally represented in airway populations from the two groups and produced IFN-gamma upon Ag stimulation in vitro. In contrast, pulmonary macrophage function was defective in TNFRI-/- mice, as indicated by a failure to up-regulate inducible NO synthase mRNA. Histopathological analysis revealed that focal infiltrates were of similar size and cell composition in the two groups but that more parasites were free of foci in the TNFRI-/- mice. These animals had a greatly impaired IgG response to schistosomes, which may explain their lack of residual protection due to Ab in a situation where cell-mediated immunity is disabled. We suggest that the absence of protective immunity could result from a retarded build-up of leukocytes around migrating lung worms and/or a deficit in accessory cell function within a focus, both of which would permit parasite escape.

Original language	English
Pages (from-to)	4489-4494
Number of pages	6
Journal	Journal of Immunology
Volume	163
Issue number	8
Publication status	Published - 15 Oct 1999

Keywords

TUMOR-NECROSIS-FACTOR
NITRIC-OXIDE SYNTHASE
LEISHMANIA-MAJOR
MICE LACKING
IRRADIATED CERCARIAE
CYTOKINE REGULATION
ANTIBODY-RESPONSES
FACTOR RECEPTOR-1
DEFICIENT MICE
FACTOR-ALPHA

Cite this

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title = "TNF is essential for the cell-mediated protective immunity induced by the radiation-attenuated schistosome vaccine",

abstract = "C57BL/6 mice exposed to the radiation-attenuated schistosome vaccine exhibit high levels of protective immunity. The cell-mediated pulmonary effector mechanism involves IFN-gamma-producing CD4(+) T cells in a focal response around challenge larvae. IFN-gamma can promote production of TNF and can synergize with this cytokine in its actions on responder cells, We have examined whether TNF plays a role in lung phase immunity to schistosomes using mice with a disrupted gene for TNFRI (TNFRI-/-). The most dramatic finding was that the schistosome vaccine elicited no protection whatsoever in these mice. However, this could not be attributed to a lack of responder cells, because more lymphocytes were lavaged from the airways of TNFRI-/- than wild-type mice. Furthermore, CD4(+) T cells were equally represented in airway populations from the two groups and produced IFN-gamma upon Ag stimulation in vitro. In contrast, pulmonary macrophage function was defective in TNFRI-/- mice, as indicated by a failure to up-regulate inducible NO synthase mRNA. Histopathological analysis revealed that focal infiltrates were of similar size and cell composition in the two groups but that more parasites were free of foci in the TNFRI-/- mice. These animals had a greatly impaired IgG response to schistosomes, which may explain their lack of residual protection due to Ab in a situation where cell-mediated immunity is disabled. We suggest that the absence of protective immunity could result from a retarded build-up of leukocytes around migrating lung worms and/or a deficit in accessory cell function within a focus, both of which would permit parasite escape.",

keywords = "TUMOR-NECROSIS-FACTOR, NITRIC-OXIDE SYNTHASE, LEISHMANIA-MAJOR, MICE LACKING, IRRADIATED CERCARIAE, CYTOKINE REGULATION, ANTIBODY-RESPONSES, FACTOR RECEPTOR-1, DEFICIENT MICE, FACTOR-ALPHA",

author = "M Street and Coulson, {P S} and C Sadler and Warnock, {L J} and D McLaughlin and H Bluethmann and Wilson, {R A}",

year = "1999",

month = oct,

day = "15",

language = "English",

volume = "163",

pages = "4489--4494",

journal = "Journal of Immunology",

issn = "0022-1767",

publisher = "American Association of Immunologists",

number = "8",

}

TY - JOUR

T1 - TNF is essential for the cell-mediated protective immunity induced by the radiation-attenuated schistosome vaccine

AU - Street, M

AU - Coulson, P S

AU - Sadler, C

AU - Warnock, L J

AU - McLaughlin, D

AU - Bluethmann, H

AU - Wilson, R A

PY - 1999/10/15

Y1 - 1999/10/15

N2 - C57BL/6 mice exposed to the radiation-attenuated schistosome vaccine exhibit high levels of protective immunity. The cell-mediated pulmonary effector mechanism involves IFN-gamma-producing CD4(+) T cells in a focal response around challenge larvae. IFN-gamma can promote production of TNF and can synergize with this cytokine in its actions on responder cells, We have examined whether TNF plays a role in lung phase immunity to schistosomes using mice with a disrupted gene for TNFRI (TNFRI-/-). The most dramatic finding was that the schistosome vaccine elicited no protection whatsoever in these mice. However, this could not be attributed to a lack of responder cells, because more lymphocytes were lavaged from the airways of TNFRI-/- than wild-type mice. Furthermore, CD4(+) T cells were equally represented in airway populations from the two groups and produced IFN-gamma upon Ag stimulation in vitro. In contrast, pulmonary macrophage function was defective in TNFRI-/- mice, as indicated by a failure to up-regulate inducible NO synthase mRNA. Histopathological analysis revealed that focal infiltrates were of similar size and cell composition in the two groups but that more parasites were free of foci in the TNFRI-/- mice. These animals had a greatly impaired IgG response to schistosomes, which may explain their lack of residual protection due to Ab in a situation where cell-mediated immunity is disabled. We suggest that the absence of protective immunity could result from a retarded build-up of leukocytes around migrating lung worms and/or a deficit in accessory cell function within a focus, both of which would permit parasite escape.

AB - C57BL/6 mice exposed to the radiation-attenuated schistosome vaccine exhibit high levels of protective immunity. The cell-mediated pulmonary effector mechanism involves IFN-gamma-producing CD4(+) T cells in a focal response around challenge larvae. IFN-gamma can promote production of TNF and can synergize with this cytokine in its actions on responder cells, We have examined whether TNF plays a role in lung phase immunity to schistosomes using mice with a disrupted gene for TNFRI (TNFRI-/-). The most dramatic finding was that the schistosome vaccine elicited no protection whatsoever in these mice. However, this could not be attributed to a lack of responder cells, because more lymphocytes were lavaged from the airways of TNFRI-/- than wild-type mice. Furthermore, CD4(+) T cells were equally represented in airway populations from the two groups and produced IFN-gamma upon Ag stimulation in vitro. In contrast, pulmonary macrophage function was defective in TNFRI-/- mice, as indicated by a failure to up-regulate inducible NO synthase mRNA. Histopathological analysis revealed that focal infiltrates were of similar size and cell composition in the two groups but that more parasites were free of foci in the TNFRI-/- mice. These animals had a greatly impaired IgG response to schistosomes, which may explain their lack of residual protection due to Ab in a situation where cell-mediated immunity is disabled. We suggest that the absence of protective immunity could result from a retarded build-up of leukocytes around migrating lung worms and/or a deficit in accessory cell function within a focus, both of which would permit parasite escape.

KW - TUMOR-NECROSIS-FACTOR

KW - NITRIC-OXIDE SYNTHASE

KW - LEISHMANIA-MAJOR

KW - MICE LACKING

KW - IRRADIATED CERCARIAE

KW - CYTOKINE REGULATION

KW - ANTIBODY-RESPONSES

KW - FACTOR RECEPTOR-1

KW - DEFICIENT MICE

KW - FACTOR-ALPHA

M3 - Article

VL - 163

SP - 4489

EP - 4494

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 8

ER -