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.
Induction of Insulitis by Adoptive Transfer With L3T4+ Lyt2− T-Lymphocytes in T-Lymphocyte–Depleted NOD Mice
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Toshiaki Hanafusa, Shigetaka Sugihara, Hiroko Fujino-Kurihara, Jun-Ichiro Miyagawa, Atsushi Miyazaki, Takayuki Yoshioka, Kentaro Yamada, Hiromu Nakajima, Hideki Asakawa, Norio Kono, Hiromi Fujiwara, Toshiyuki Hamaoka, Seiichiro Tarui; Induction of Insulitis by Adoptive Transfer With L3T4+ Lyt2− T-Lymphocytes in T-Lymphocyte–Depleted NOD Mice. Diabetes 1 February 1988; 37 (2): 204–208. https://doi.org/10.2337/diab.37.2.204
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