CD44 gene vaccination for insulin-dependent diabetes mellitus in non-obese diabetic mice.
BACKGROUND
Standard CD44 and its alternatively spliced variants were found to be associated with the metastatic potential of tumor cells and with cell migration of autoimmune inflammatory cells, including cells involved in experimental insulin-dependent diabetes mellitus.


OBJECTIVE
To investigate whether induction of anti-CD44 immune reactivity, through cDNA vaccination, could attenuate IDDM in a transfer model of NOD mice.


METHODS
Our vaccination technique involved the insertion of CD44s or CD44v cDNA into a silicone tube filled with a 2.5 cm long segment of hydroxylated-polyvinyl acetate wound dressing sponge (forming a virtual lymph node) which was implanted under the skin of male NOD recipients reconstituted with diabetogenic spleen cells of female NOD donors. The VLN were implanted 20 days before and 3 days after cell transfer.


RESULTS
In contrast to control groups of recipient mice, recipients vaccinated with VLN loaded with CD44v or CD44s cDNAs developed resistance to IDDM almost to the same extent. Our results suggest that the gene vaccination effect was mediated by anti-CD44 antibody rather than by cellular immunity. Histopathological examinations revealed a significant protection of pancreatic islets in the DNA-vaccinated recipients, whereas the islets of control recipients of diabetogenic cells were almost totally destroyed.


CONCLUSIONS
These findings may open new opportunities for IDDM therapy in the future.
Weiss
Lola
L
Department of Bone Marrow Transplantation and Cancer Research Laboratory, Hadassah University Hospital, Jerusalem, Israel.
Botero-Anug
Ana Maria
AM
Hand
Carla
C
Slavin
Shimon
S
Naor
David
D
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D018960:Hyaluronan Receptors / Q000235:genetics* / Q000276:immunology; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D051379:Mice; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA
D018960:Hyaluronan Receptors; D019444:Vaccines, DNA