TISSUE CULTURE OF THE ISLETS OF LANGERHANS

Project: Research project

Description

The major objectives of this proposal are to continue studies on the
prevention of rejection of adult islet allografts in rodents, adult islet
allografts in rodents without the continuous use of immunosuppressive drugs
in the recipients. We have shown that rejection of islet allografts in
mice can be prevented by in vitro treatment of donor mouse islets with a
specific Ia antibody or a monoclonal antibody to mouse dendritic cells and
complement and preimmunization of recipient mice with donor blood depleted
of Ia+ cells. We have shown that rejection of islet allografts in rats can
be prevented by low temperature culture (24 C) and a single injection of
ALS into the recipient. We will attempt to prevent rejection of rat islet
allografts by treatment of donor islets with cross-reactive Ia antibodies
or by monoclonal antibodies to rat dendritic cells. Studies are also in
progress to determine whether specific suppressor lymphoid cells have been
induced in mice bearing established islet allgrafts. A model has been
developed for the induction of T suppressor cells inhibiting the in vitro
generation of cytotoxic T lymphocytes by treatment of mice with cyclosporin
A and allogeneic spleen cells. This model will be tested for prevention of
rejection of islet allografts and xenografts. We have shown that
xenografts across a closely related species barrier (rat to mouse) can be
prevented from rejecting by low temperature culture and a single injection
of ALS. We will determine whether xenografts of islets transplanted across
a wide species barrier (beef, dog, pig or hamster to rat or mouse
recipients) can be prevented from rejecting using the procedures that have
prevented rejection of islet allografts in rodents. The procedures that we
have developed for prevention of rejection of adult islet allografts will
also be used to determine whether these methods will prevent rejection of
fetal pancreas allografts. These investigations on preventing rejection of
islet allografts and xenografts without using immunosuppressive drugs are
of importance to utilizing islet transplantation in human diabetes and the
transplantation of other tissues and organs.
StatusFinished
Effective start/end date5/1/784/30/90

Funding

  • National Institutes of Health

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Allografts
Heterografts
Rodentia
Immunosuppressive Agents
Dendritic Cells
Monoclonal Antibodies
Tissue Donors
Islets of Langerhans Transplantation
Temperature
Cytotoxic T-Lymphocytes
Blood Donors
Cricetinae
Pancreas
Swine
Therapeutics
Spleen
Dogs
Lymphocytes
Injections
Antibodies