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Induction of oral tolerance in a murine model of chronic graft versus host disease ameliorates disease manifestation
Year:
1998
Source of publication :
Experimental Hematology
Authors :
Pines, Mark
;
.
Volume :
26
Co-Authors:

Nagler, A.
Pines, M.
Abadi, U.
Pappo, Q.
Zeira, M.
Roy Chowdhurv, N.
Rov Chowdhury, J.
Llan, Y.

Facilitators :
From page:
777
To page:
0
(
Total pages:
-776
)
Abstract:
Chronic graft versus host disease (cGVHD) is an autoimmune-like disorder resulting in skin manifestations resembling scleroderma. Induction of immunological hyporesponsiveness to orally administered antigens have been recently shown to suppress autoimmunity in several animal models. We studied the feasibility of inducing oral tolerance and ameliorate disease manifestation in a cGVHD mice model. cGVHD was induced by administration of splenocytes (25xl06) from B10.D2 to sublethaly irradiated (600Gy) Balb/c mice, across minor histocompatibility antigens (H-2 , mlsb). In this model cGVHD is manifested by scleroderma like skin lessions, fibrös is, increase in skin collagen, and loss of subdermal fat, weight loss, and severe liver inflammation. Oral tolerance was induced by feeding B10.D2 donor mice with Balb/c recipient splenocyte protein extract at a dose of 50u,g/mice for 11 days prior to transplantation. Induction of tolerance was documented by significant reduction in the MLR response of tolerated versus non tolerated effector B10.12 splenocytes against Balb/c stimulators, respectively (24,000 versus 8,000 cpm) (n=3) (p<0.01). Induction of oral tolerance prevented weight loss and resulted in significant reduction in skin collagen content and gene expression evaluated by immunohistochemistry and in situ hybridization using collagen a 1(1) probe. It also prevented dermal thickening and loss of subdermal fat. Liver biopsies disclosed marked reduction in inflammatory response. Serum IL-10 levels were significantly higher in the tolerized mice (108.5 versus 46.5 pg/ml) while IFN-ct, IL-2 and TNF-a were significantly lower than the controls 10,11 a 2.5pg/ml vs 75.3, 22 a and I6.5pg/ml, respectively (n=3) (p<0.005). In summary, induction of oral tolerance resulted in a shift from Th 1 proinflammatory to a Th2 anti-inflammatory cytokine profile, downregulating the immune response and ameliorating cGVHD.
Note:
Related Files :
autoimmune diseases
chronic graft versus host disease
Health and pathology
immune response
immune system
Mice models
skin
Show More
Related Content
More details
DOI :
Article number:
0
Affiliations:

From the Liver Unit, Department of Medicine, and Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel; Institute of Animal Science, Agricultural Research Organization, The Volcani Center, Beit Dagan, Israel; and ENZO Biochem Inc, New York, NY.

Database:
Scopus
Publication Type:
article
;
.
Language:
English
Editors' remarks:
ID:
26100
Last updated date:
02/03/2022 17:27
Creation date:
17/04/2018 00:20
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Scientific Publication
Induction of oral tolerance in a murine model of chronic graft versus host disease ameliorates disease manifestation
26

Nagler, A.
Pines, M.
Abadi, U.
Pappo, Q.
Zeira, M.
Roy Chowdhurv, N.
Rov Chowdhury, J.
Llan, Y.

Induction of oral tolerance in a murine model of chronic graft versus host disease ameliorates disease manifestation
Chronic graft versus host disease (cGVHD) is an autoimmune-like disorder resulting in skin manifestations resembling scleroderma. Induction of immunological hyporesponsiveness to orally administered antigens have been recently shown to suppress autoimmunity in several animal models. We studied the feasibility of inducing oral tolerance and ameliorate disease manifestation in a cGVHD mice model. cGVHD was induced by administration of splenocytes (25xl06) from B10.D2 to sublethaly irradiated (600Gy) Balb/c mice, across minor histocompatibility antigens (H-2 , mlsb). In this model cGVHD is manifested by scleroderma like skin lessions, fibrös is, increase in skin collagen, and loss of subdermal fat, weight loss, and severe liver inflammation. Oral tolerance was induced by feeding B10.D2 donor mice with Balb/c recipient splenocyte protein extract at a dose of 50u,g/mice for 11 days prior to transplantation. Induction of tolerance was documented by significant reduction in the MLR response of tolerated versus non tolerated effector B10.12 splenocytes against Balb/c stimulators, respectively (24,000 versus 8,000 cpm) (n=3) (p<0.01). Induction of oral tolerance prevented weight loss and resulted in significant reduction in skin collagen content and gene expression evaluated by immunohistochemistry and in situ hybridization using collagen a 1(1) probe. It also prevented dermal thickening and loss of subdermal fat. Liver biopsies disclosed marked reduction in inflammatory response. Serum IL-10 levels were significantly higher in the tolerized mice (108.5 versus 46.5 pg/ml) while IFN-ct, IL-2 and TNF-a were significantly lower than the controls 10,11 a 2.5pg/ml vs 75.3, 22 a and I6.5pg/ml, respectively (n=3) (p<0.005). In summary, induction of oral tolerance resulted in a shift from Th 1 proinflammatory to a Th2 anti-inflammatory cytokine profile, downregulating the immune response and ameliorating cGVHD.
Scientific Publication
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