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Cellular and genetic factors involved in the difference between Brown Norway and Lewis rats to develop respectively type‐2 and type‐1 immune‐mediated diseases
Author(s) -
Fournié Gilbert J.,
Cautain Bastien,
Xystrakis Emmanuel,
Damoiseaux Jan,
Lagrange Magali Mas Dominique,
Bernard Isabelle,
Subra JeanFrançois,
Pelletier Lucette,
Druet Philippe,
Saoudi Abdelhadi
Publication year - 2001
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1034/j.1600-065x.2001.1840114.x
Subject(s) - immune system , immunology , biology , autoimmune disease , experimental autoimmune encephalomyelitis , cd8 , autoimmunity , major histocompatibility complex , t cell , genetics , antibody
Summary: The understanding of the mechanisms of immune tolerance and the unravelling of the pathophysiology of autoimmune diseases rely on animal models. In this respect, BN and LEW rats represent models of choice to study immune‐mediated diseases from the cellular and genetic points of view. Indeed, BN and LEW rats are extremes with respect to their polarisation of the immune response as well as their susceptibility to autoimmune diseases. LEW rats are susceptible to Th1‐mediated autoimmune diseases while BN rats are highly susceptible to Th2‐mediated autoimmune disease. Comparison of the T cell compartment between LEW and BN rats revealed several important differences. 1) A MHC‐dependent quantitative difference that is due to a defect in the CD8 T cell compartment in BN rats. 2) A qualitative MHC‐independent difference that is related to a high frequency of CD45RC low CD4 and CD8 T cell subsets, producing IL‐4, IL‐13, IL‐10 and TGF‐β in BN rats as compared to LEW rats. 3) Interestingly, the genetic studies showed that susceptibility to Th1‐mediated experimental autoimmune encephalomyelitis, and to Th2‐mediated disorders triggered by gold salts as well as the difference in the CD45RC high /CD45RC low ratio between LEW and BN rats are genetically determined by regions on chromosomes 9, 10 and 20.