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 resp onse to the secretory granule protein tyrosine phosphatase (PTP), phogrin w as evaluated by immunization of 8- to 12-week-old animals with recombinant phogrin in complete Freund's adjuvant. Draining lymph nodes displayed a rob ust 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 V beta usage. Of th e 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 ad jacent thyroid implants. The results demonstrate the feasibility of generat ing antigen-specific diabetes-inducing CD4(+) cells by direct immunization of NOD mice and their potential use for further studies of the antigenic ep itopes in the PTP family members. The conclusion, based on serological stud ies, that PTP members do not play a role in the pathogenesis of type 1 diab etes in rodent models needs reevaluation in light of these findings.