Cellular immune response to phogrin in the NOD mouse: cloned T-cells cause destruction of islet transplants.
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 Vbeta 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.
Kelemen
K
K
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver 80262, USA.
Crawford
M L
ML
Gill
R G
RG
Hutton
J C
JC
Wegmann
D
D
D000818:Animals; D002455:Cell Division / Q000502:physiology; D002999:Clone Cells; D003921:Diabetes Mellitus, Experimental / Q000601:surgery; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D005260:Female; D007111:Immunity, Cellular / Q000502:physiology*; D007114:Immunization; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D008565:Membrane Proteins; D051379:Mice; D016688:Mice, Inbred NOD / Q000276:immunology*; D016513:Mice, SCID; D010641:Phenotype; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000276:immunology*; D051381:Rats; D011919:Rats, Inbred Strains; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000502:physiology; D014183:Transplantation, Heterologous
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011994:Recombinant Proteins; C102889:PTPRN2 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8