TY - JOUR
T1 - Cellular immune response to phogrin in the NOD mouse
T2 - Cloned T-cells cause destruction of islet transplants
AU - Kelemen, Katalin
AU - Crawford, Megan L.
AU - Gill, Ronald G.
AU - Hutton, John C.
AU - Wegmann, Dale
PY - 1999/8
Y1 - 1999/8
N2 - The ability of nonobese diabetic (NOD) mice to mount a cellular immune response to the secretory granule protein tyrosine phosphatase (PTP), phogrin was evaluated by immunization of 8- to 12-week-old animals with recombinant phogrin in complete Freund's adjuvant. Draining lymph nodes displayed a robust proliferative response to the protein, as did derived T-cell lines and clones. Ten clones obtained by limiting dilution were all CD4+ and of a T- helper-1-like phenotype, but showed variation in their Vβ usage. Of the 10 clones, 3 responded to endogenous antigens in rat islets. Two of these caused the destruction of rat islets that had been transplanted under the kidney capsule of streptozotocin-treated NOD scid mice without affecting adjacent thyroid implants. The results demonstrate the feasibility of generating antigen-specific diabetes-inducing CD4+ cells by direct immunization of NOD mice and their potential use for further studies of the antigenic epitopes in the PTP family members. The conclusion, based on serological studies, that PTP members do not play a role in the pathogenesis of type 1 diabetes in rodent models needs reevaluation in light of these findings.
AB - The ability of nonobese diabetic (NOD) mice to mount a cellular immune response to the secretory granule protein tyrosine phosphatase (PTP), phogrin was evaluated by immunization of 8- to 12-week-old animals with recombinant phogrin in complete Freund's adjuvant. Draining lymph nodes displayed a robust proliferative response to the protein, as did derived T-cell lines and clones. Ten clones obtained by limiting dilution were all CD4+ and of a T- helper-1-like phenotype, but showed variation in their Vβ usage. Of the 10 clones, 3 responded to endogenous antigens in rat islets. Two of these caused the destruction of rat islets that had been transplanted under the kidney capsule of streptozotocin-treated NOD scid mice without affecting adjacent thyroid implants. The results demonstrate the feasibility of generating antigen-specific diabetes-inducing CD4+ cells by direct immunization of NOD mice and their potential use for further studies of the antigenic epitopes in the PTP family members. The conclusion, based on serological studies, that PTP members do not play a role in the pathogenesis of type 1 diabetes in rodent models needs reevaluation in light of these findings.
UR - http://www.scopus.com/inward/record.url?scp=0032768786&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032768786&partnerID=8YFLogxK
U2 - 10.2337/diabetes.48.8.1529
DO - 10.2337/diabetes.48.8.1529
M3 - Article
C2 - 10426369
AN - SCOPUS:0032768786
SN - 0012-1797
VL - 48
SP - 1529
EP - 1534
JO - Diabetes
JF - Diabetes
IS - 8
ER -