RGD Reference Report - Prevention of autoimmune diabetes in the DRBB rat by CD40/154 blockade. - Rat Genome Database

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Prevention of autoimmune diabetes in the DRBB rat by CD40/154 blockade.

Authors: Moore, WV  Chu, W  Tong, PY  Hess, D  Benjamin, C  Khalili, J  Kover, K 
Citation: Moore WV, etal., J Autoimmun. 2002 Nov;19(3):139-45.
RGD ID: 8547798
Pubmed: PMID:12419284   (View Abstract at PubMed)

The autoimmune diabetes of the DRBB rat shares important similarities with autoimmune diabetes in humans. We have tested the ability of CD40/154 blockade using an anti-CD154 antibody (AH.F5) to prevent autoimmune diabetes in DRBB rats. The rats were treated with two intravenous doses/wk of AH.F5 (15mg/kg/dose) starting at 2-6wks of age. RT6.1 T-cell depletion and poly I/C was started at 4wks of age. Control rats developed diabetes within 25 days after start of depletion therapy. Six of 7, 11 of 13, 7 of 12, and 4 of 11 rats treated with AH.F5 did not develop diabetes when treatment was started at 2-3, 4, 5, and 6wks of age, respectively. The rats that did not develop diabetes were maintained for a minimum of 72 days to >150 days following the last dose of AH.F5. Eleven rats maintained for >150 days underwent an additional depletion and 5/11 developed diabetes within 8-19 days following start of depletion.Histological examination indicated that AH.F5 prevented and possibly reversed insulitis. Islets in about 50% of the treated rats remained free of inflammation following a second course of RT 6.1 T-cell depletion after the serum concentration of AH.F5 was negligible. In summary, CD40/154 blockade with AH.F5 prevents development of autoimmune diabetes if treatment is started prior to overt signs of beta cell destruction. The results indicate that the CD40/154 blockade can prevent diabetes by modifying the expansion or effector phase of the autoimmune diabetes.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
type 1 diabetes mellitus treatmentISOCd40lg (Rattus norvegicus)8547798; 8547798 RGD 
type 1 diabetes mellitus treatmentIMP 8547798 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cd40lg  (CD40 ligand)

Genes (Mus musculus)
Cd40lg  (CD40 ligand)

Genes (Homo sapiens)
CD40LG  (CD40 ligand)


Additional Information