Quantitative phenotypic and functional analyses of islet immune cells before and after diabetes onset in the BB rat

N. Hosszufalusi, E. Chan, M. Teruya, S. Takei, G. Granger, M. A. Charles

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10 Citations (Scopus)

Abstract

Inflammatory cells invading islets are thought to be mediators of islet destruction in spontaneous autoimmune diabetes mellitus. Thus methods were developed to isolate and characterize in situ islet inflammatory cells from 75-95-day-old prediabetic and diabetic BB rats. Islet inflammatory cells were structurally examined using single- and double-colour flow cytometry. Functional studies consisted of cytolytic assays using normal rat islet target cells and in situ islet or spleen effector cells. Structural data reveal natural killer cells to be the major cell population (70%) of total immune cells present in inflamed islets during prediabetes. At diabetes onset, the natural killer cell population remained at a high level (47%), but an increasing population of T cells (40%) was noted also. Analyses of T-cell subsets before and after diabetes onset revealed CD4+ T cells as predominant (50-55% of total T cells) with double-negative (CD4- CD8-) T cells (25-30%) and CD8+ T cells (15-20%) also present in significant quantities. Activated T cells accounted only for a minority of T cells (<3%). Functional studies indicate that in situ islet-derived cytolytic effector cells are more potent killers (ten-fold) of normal islet target cells than are splenic effector cells. These data suggest that in situ islet inflammatory cells (a) can be quantitatively studied both structurally and functionally; (b) express structural phenotypes differing substantially from splenic mononuclear cell populations; (c) are considerably more cytolytic than splenic effectors; and (d) should prove informative in determining the most significant autoimmune functional events prior to and during islet beta-cell destruction.

Original languageEnglish
Pages (from-to)1146-1154
Number of pages9
JournalDiabetologia
Volume36
Issue number11
DOIs
Publication statusPublished - Nov 1 1993

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Keywords

  • BB rat
  • diabetes mellitus
  • in situ islet immune cells
  • inflamed islets
  • islets

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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