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.
Hanafusa
T
T
Second Department of Internal Medicine, Osaka University Medical School, Japan.
Sugihara
S
S
Fujino-Kurihara
H
H
Miyagawa
J
J
Miyazaki
A
A
Yoshioka
T
T
Yamada
K
K
Nakajima
H
H
Asakawa
H
H
Kono
N
N
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology; D003920:Diabetes Mellitus / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000235:genetics / Q000473:pathology; D005260:Female; D007116:Immunization, Passive; D007150:Immunohistochemistry; D007515:Islets of Langerhans; D008198:Lymph Nodes / Q000166:cytology / Q000637:transplantation; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009765:Obesity; D010182:Pancreatic Diseases / Q000209:etiology; D013154:Spleen / Q000166:cytology / Q000637:transplantation; D013601:T-Lymphocytes / Q000473:pathology / Q000637:transplantation*