Increased islet antigen presentation leads to type-1 diabetes in mice with autoimmune susceptibility.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is frequently used in preclinical and clinical protocols to modulate autoimmune responses, bone marrow transplants, and recovery from immune ablative therapies. The immunological outcome of such therapies is not fully understood. We tested the hypothesis that GM-CSF would enhance the maturation of antigen-presenting cells, facilitating presentation of beta-cell autoantigens to autoreactive T cells. We found that islet expression of GM-CSF greatly enhanced disease in male mice. Islet-derived APC but not splenic APC showed markedly enhanced capacity to stimulate in vitro proliferative responses of islet-antigen-specific autoreactive T cells. In vivo transfer of CD8(+) and CD4(+) T cells demonstrate that autoreactive T cells undergo extensive division in pancreatic lymph nodes of GM-CSF-transgenic mice compared with wild-type NOD male mice. Together, the results presented here demonstrate that expression of GM-CSF in the pancreas can enhance autoimmunity in disease-susceptible mice.
Judkowski
Valeria
V
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Krakowski
Michelle
M
Rodriguez
Enrique
E
Mocnick
Lorraine
L
Santamaria
Pere
P
Sarvetnick
Nora
N
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D013154:Spleen / Q000166:cytology / Q000276:immunology
D016178:Granulocyte-Macrophage Colony-Stimulating Factor