6 research outputs found
Functional status of the immune system after chronic administration of 2'-deoxycoformycin in the BB rat
Insulin-dependent diabetes mellitus (IDDM)
is caused by autoimmune destruction of pancreatic beta
cells with the primary mechanism being cell mediated.
The BB rat develops insulitis and IDDM with many
features analogous to the disease in man. In previous
studies we reported that weekly administration of 2'-
deoxycoformycin (dCF) for four months reduces
significantly the incidence of IDDM in the BB rat by
70%, and that the animals remain free of diabetes for a
minimum of two months after drug withdrawal. Since
the diabetes-prone BB rat is lymphopenic, with a
reduction of both CD4 and CD8 cells, the continuous
failure of dCF treated animals to develop diabetes may
have been due to generalized immunosuppression. To
test this possibility, the ability of dCF treated diabetesfree
BB rats to mount an immune response after
challenge with Ovalbumin was examined five months
after drug withdrawal. The results showed that the postimmunization
levels of total IgG and specific IgG in
these animals did not differ from those observed in nondCF
treated controls nor those of control diabetesresistant
non-lymphopenic BB rats. Moreover, FACS
analysis indicated no change in the percentages or total
numbers of CD4t or CD8+ cells between the two groups
of animals. Histological assessment of the pancreata of
the post-dCF treated animals showed varying degrees of
mononuclear cell infiltrates in the islets. These data
demonstrate that treatment by dCF is not permanent, and may require intermittent or continuous administration to
prevent development of diabetes. Further studies are
needed to determine the mechanism of action of dCF in
this model of IDDM