Induction of Insulitis by Adoptive Transfer With L3T4⁺ Lyt2⁻ T-Lymphocytes in T-Lymphocyte–Depleted NOD Mice

To clarify the pathogenesis of insulitis in the nonobese diabetic (NOD) mouse, an animal model for human insulin-dependent diabetes mellitus, T-lymphocyte-depleted NOD mice (B mice) were adoptively transferred with spleen and lymph node cells from cyclophosphamide-treated NOD mice after separating the cells with monoclonal antibodies against various T-lymphocyte surface antigens plus complement. Light-microscopic and immunohistochemical studies were also performed to investigate the lymphocytic infiltrations. The incidence of insulitis detected in B mice was much lower when compared with that of the lesion naturally occurring in the NOD mouse. However, higher incidence of insulitis was inducible in B mice by transferring unfractionated lymphoid cells from NOD mice. When the Thy1⁺ cell-depleted fraction was transferred into the B mice, no increase in the incidence of insulitis was observed. The Lyt1⁺ or L3T4⁺ cell-eliminated fraction was also unable to transfer insulitis. Conversely, donor cells depleted of Lyt2⁺ components successfully induced insulitis in the recipient B mice. These data were consistent with the immunohistochemical study, which showed that the main phenotype of the cells infiltrating the islets was L3T4⁺. These results suggest the importance of L3T4⁺Lyt2⁻ T-lymphocytes in the pathogenesis of insulitis in NOD mice.