Macrophage infiltration precedes and is a prerequisite for lymphocytic insulitis in pancreatic islets of pre-diabetic BB rats.
We have analysed whether infiltration of macrophages and lymphocyte subtypes into pancreatic islets of diabetes prone BB rats occurs at random or whether insulitis requires a specific sequence of events. Serial sections from more than 700 islets of diabetes prone BB rats (70-150 days of age) were analysed for infiltrating immunocytes and expression of major histocompatibility complex antigens by 4-11 different monoclonal antibodies. In parallel, electron microscopy was performed in a fraction of islets. Part of the animals had been treated with macrophage toxic silica particles. A specific non-random sequence of events was identified and 4 stages of islet inflammation were recognised. Stages 1a and 1b are defined by macrophage (ED1+, W3/25+. Ox3/6/17+, ED2-) infiltration and concomitant enhanced major histocompatibility complex class I antigen expression initially at one pole or at the periphery of islets. T-, NK- and B-lymphocytes are absent (less than 1 cell per mean islet section). In stage 2, more macrophages are infiltrating and concomitantly Ox19+-T-lymphocytes and Ox8+-granular (NK-) lymphocytes are observed. In stage 3, additional massive infiltration of Ox12+-B-lymphocytes is noted. Silica treatment of BB rats largely prevented macrophage infiltration. Concomitantly islets were free of lymphocytes. Thus, macrophage infiltration clearly precedes T- and NK-lymphocyte and later B-lymphocyte infiltration. Lymphocytes do not infiltrate islets in the absence of prior macrophage invasion.
Hanenberg
H
H
Diabetes Research Institute, University of Düsseldorf, FRG.
Kolb-Bachofen
V
V
Kantwerk-Funke
G
G
Kolb
H
H
D000818:Animals; D000911:Antibodies, Monoclonal; D003921:Diabetes Mellitus, Experimental / Q000276:immunology* / Q000473:pathology; D006680:HLA Antigens / Q000032:analysis*; D007074:Immunoglobulin G / Q000032:analysis / Q000145:classification*; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology / Q000648:ultrastructure; D008214:Lymphocytes / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology / Q000648:ultrastructure; D008854:Microscopy, Electron; D011236:Prediabetic State / Q000276:immunology* / Q000473:pathology; D051381:Rats; D011913:Rats, Inbred BB
D000911:Antibodies, Monoclonal; D006680:HLA Antigens; D007074:Immunoglobulin G