ABSTRACT
To investigate the effects of recipient age on the induction of diabetes by CD4+ islet-specific T-cell clones, we tested four different clones in non-obese diabetic (NOD) mice of different ages. Transfer of each of the T-cell clones resulted in insulitis and full development of diabetes in unirradiated 8-18-day-old NOD mice within 2-3 weeks. A small gender bias in disease susceptibility was seen in 8-14-day-old female NOD mice, which showed a twofold increase in disease incidence over both age-matched males and slightly older (15-18-day-old) females. In contrast, both male and female NOD mice, 19 days or older, were highly resistant to T-cell clone-induced insulitis and completely resistant to the development of diabetes. In mice of an intermediate age range (15-18 days old), two of the clones showed a three- to fourfold reduction in transfer of overt diabetes regardless of gender. These results suggest that an important developmental event occurs in both male and female NOD mice between the age of 15 and 19 days, leading to the inhibition of disease induced by T-cell clones.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , Diabetes Mellitus, Type 1/immunology , Islets of Langerhans/immunology , Age Factors , Animals , Clone Cells/immunology , Diabetes Mellitus, Type 1/pathology , Disease Susceptibility , Female , Kinetics , Lymphocyte Transfusion , Male , Mice , Mice, Inbred NOD , Sex FactorsABSTRACT
Identification of diabetes-associated T-cell autoantigens is important for understanding the immunopathology of diabetes and developing improved therapeutic strategies. We have used a genetic approach to move toward identifying the autoantigen recognized by a diabetogenic islet-specific T-cell clone from a nonobese diabetic (NOD) mouse. The unique antigen recognition pattern of this clone was utilized to map the gene encoding the antigen (or its expression) by genetic linkage analysis. In vitro analysis of T-cell proliferation by this clone showed that the capacity of the islets to stimulate T cells segregates as a single codominant gene in BALB/cByJ x (BALB/cByJ x NOD/Bdc) backcross mice. This phenotype was tightly linked to two microsatellites in the telomeric region of mouse chromosome 6.
