Coexpression of B7-1 and viral ("self") transgenes in pancreatic beta cells can break peripheral ignorance and lead to spontaneous autoimmune diabetes

Immunity. 1995 Dec;3(6):727-38. doi: 10.1016/1074-7613(95)90062-4.

Abstract

We evaluated the role of the costimulatory molecule B7-1 in overcoming peripheral ignorance in transgenic mice, which expressed the glycoprotein (GP) or nucleoprotein (NP) of lymphocytic choriomeningitis virus (LCMV) as the self-antigen in pancreatic beta cells. The viral transgenes or B7-1 alone did not induce autoimmune diabetes (IDDM). However, in bigenic mice expressing B7-1 and LCMV-GP, anti-self (viral) cytotoxic T lymphocytes (CTL) were activated without viral infection and spontaneous IDDM occurred. In contrast, bigenic RIP-B7-1 x RIP-NP mice with thymic expression of the self (viral-NP) antigen deleted the majority of their autoreactive CTL and did not develop spontaneous IDDM. However, these mice developed fast-onset IDDM 14 days after LCMV infection, whereas single-transgenic RIP-NP littermates developed IDDM only within 4-5 months. Rapid IDDM was associated with increased numbers of anti-self CTL and a predominance of IFN gamma produced by islet-infiltrating lymphocytes, whereas single transgenic RIP-NP littermates with slow-onset IDDM displayed less anti-self CTL and more IL-4- and IL-10-producing T lymphocytes in pancreatic infiltrates.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Viral / immunology
  • B7-1 Antigen / biosynthesis*
  • B7-1 Antigen / genetics
  • B7-1 Antigen / immunology
  • Diabetes Mellitus, Type 1 / etiology
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / metabolism*
  • Glycoproteins / biosynthesis*
  • Glycoproteins / genetics
  • Glycoproteins / immunology
  • Islets of Langerhans / immunology
  • Islets of Langerhans / metabolism*
  • Lymphocyte Activation
  • Lymphocytic choriomeningitis virus / genetics
  • Lymphocytic choriomeningitis virus / immunology
  • Lymphocytic choriomeningitis virus / metabolism*
  • Mice
  • Mice, Transgenic
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Antigens, Viral
  • B7-1 Antigen
  • Glycoproteins