Marked dendritic cell-T cell cluster formation in the pancreatic lymph node of the non-obese diabetic mouse.
Dendritic cells (DC) isolated from various lymph node (LN) groups of pre-diabetic non-obese diabetic (NOD) (4-20 weeks of age) and age-sex-matched control mice were analysed for their surface antigen phenotype and their ability to cluster lymphocytes. The draining LN of the pancreas (PLN) of 8-week-old NOD mice with active autoimmune disease were significantly enlarged in comparison to the axillary LN of the same NOD mice and the PLN from control mice. NOD DC isolated from PLN and other LN demonstrated classical DC morphology, were highly major histocompatibility complex (MHC) class II antigen positive, and were 50-70% 33D1+ (DC-specific antibody). In an assay for DC-T cell clustering, DC from the PLN of 8-20-week-old NOD formed large clusters (greater than 10 cells) with PLN cells at a frequency three to 20 times greater than that observed with DC and LN cells from the PLN of 8-week-old control mice, the PLN of 4-week-old NOD mice, and axillary/inguinal LN of 8-week-old NOD mice. Clustered cells were 80% Thy-1.2+ (56% L3T4, 17% Lyt-2+). Specificity of clustering was demonstrated as PLN DC clustered only PLN T cells in the assay; axillary/inguinal (A/I) DC added to PLN LC did not induce clustering nor did PLN DC induce clustering of the A/I population. Cell proliferation in isolated PLN DC/LC clusters was markedly greater than that of A/I clusters and of non-clustered PLN cells. These data demonstrate that DC from the PLN of NOD mice with active autoimmune disease form stable clusters with T cells from the PLN and these clusters are the major source of proliferating T cells in these LN. We hypothesize that PLN DC may play an important role in the autoimmune disease of the NOD mouse.
Department of Medicine, University of California, Los Angeles 90024.
M
M
Clare-Salzler
Y
Y
Mullen
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002448:Cell Adhesion / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D007075:Immunoglobulin M / Q000032:analysis; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000033:anatomy & histology / Q000166:cytology*; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D016688:Mice, Inbred NOD; D009929:Organ Size; D010179:Pancreas; D013601:T-Lymphocytes / Q000502:physiology*; D018800:Thy-1 Antigens
D000954:Antigens, Surface; D015704:CD4 Antigens; D016827:CD8 Antigens; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D018800:Thy-1 Antigens