Pancreatic lymph nodes are early targets of T cells during adoptive transfer of diabetes in NOD mice.
The circulation pathway of diabetogenic T lymphocytes prior to insulitis was investigated using adoptive transfer of diabetes in the non-obese diabetic (NOD) mouse model. Transferred T cells were distinguished from recipient T cells using two strains of mice congenic at the Thy1 locus. They were monitored in the pancreas and in several lymphoid organs including thymus, spleen, and lymph nodes from pancreatic, mesenteric, axillary, inguinal and lomboaortic areas, from Day 0 to Day 15 after the adoptive lymphocytic transfer. Immunohistochemical studies showed that at Day 2 post-transfer the pancreatic lymph nodes (PLN) and to a lesser extent the spleen, are the first two organs to be infiltrated. The amount of T cells of donor origin using quantitative flow cytometric analysis was 4% and 2.6% respectively. This percentage increased to 19% in the PLN at Day 15 and did not exceed 7% in the spleen. Analysis of the expression of IL-2 receptor present at the surface of activated T lymphocytes showed that 73% of donor T cells were activated in the PLN within 3 days post-transfer in contrast to 0% in the spleen. The accumulation and activation of T cells in the PLN may imply a role of these lymphoid organs in harbouring the diabetogenic T cells during the early steps of the disease.
Fabien
N
N
Inserm U. 197, Faculté de Médecine Alexis Carrel, Lyon, France.
Bergerot
I
I
Maguer-Satta
V
V
Orgiazzi
J
J
Thivolet
C
C
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000032:analysis; D007518:Isoantibodies; D017493:Leukocyte Common Antigens / Q000032:analysis; D008198:Lymph Nodes / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000276:immunology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation*
D007376:Interleukin-2; D007518:Isoantibodies; D015375:Receptors, Interleukin-2; C035678:anti-Thy antibody; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D001973:Bromodeoxyuridine