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.
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 CD45RClow CD4 and CD8 T cell subsets, producing IL-4, IL-13, IL-10 and TGF-beta 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 CD4SRChigh/CD45RClow ratio between LEW and BN rats are genetically determined by regions on chromosomes 9, 10 and 20.
Fournié
G J
GJ
Institut National de la Santé et de la Recherche Médicale (INSERM) U28, Hôpital Purpan, Université Paul Sabatier, Toulouse, France.
Cautain
B
B
Xystrakis
E
E
Damoiseaux
J
J
Mas
M
M
Lagrange
D
D
Bernard
I
I
Subra
J F
JF
Pelletier
L
L
Druet
P
P
Saoudi
A
A
D000818:Animals; D004198:Disease Susceptibility / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006801:Humans; D017493:Leukocyte Common Antigens / Q000276:immunology; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D051381:Rats; D011914:Rats, Inbred BN / Q000235:genetics* / Q000276:immunology*; D011917:Rats, Inbred Lew / Q000235:genetics* / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1