TY - JOUR
T1 - An mrl/mpj-/pr//pr substrain with a limited expansion of ipr double-negative t cells and a reduced autoimmune syndrome
AU - Fossati, Liliane
AU - Takahashi, Satoru
AU - Merino, Ramon
AU - Iwamoto, Masahiro
AU - Aubry, Jean Pierre
AU - Nose, Masato
AU - Spach, Colette
AU - Motta, Roland
AU - Izui, Shozo
N1 - Funding Information:
We thank Ms Genevieve Leyvraz for her excellent technical help and Mr D. Wohlwend (Cytofluorography Unit, Faculty of Medicine, University of Geneva) for his help with flow cytometry. This work was supported by a grant 31-28782.90 from the Swiss National Foundation for Scientific Research and by Scientific Research Funds from the Ministry of Education, Science and Culture of Japan. R.M. is a recipient of a grant from 'Servicio de Formacion de Personal Investigador, Ministerio de Educacion y Ciencia, Spain'.
PY - 1993/5
Y1 - 1993/5
N2 - The autosomal recessive mutant gene, Ipr, has been shown to accelerate the progression of lupus-like autoimmune disease, which is associated with a massive expansion of a unique CD4˜CD8˜ double-negative T cell subset, in MRL/MpJ mice. Here we report a substrain of MRL/MpJ-fpr//pr (MRL-fpr) mice which live almost twice as long with delayed development of glomerulonephritis, compared with conventional MRL-/pr mice. This substrain, termed MRL-/pr.//(//for long-lived), develops generalized lymphadenopathy characteristically seen in MRL-/pr mice. However, the expansion of a double negative Ipr T cell subset is markedly limited with a mean value of 15% in their lymph nodes compared to about 70% in conventional MRL-/pr mice. Overall production of autoantibodies, such as anti-DNA and rheumatoid factors, does not significantly differ between the two MRL-/pr mice. However, serum levels of cryoglobulins, whose major component is lgG3, are markedly diminished in MRL-/pr.//mice with a parallel decrease in lgG3. Since MRL-/pr.//mice still carry the Ipr mutation, as documented by the presence of defects in the Fas antigen, a possible new mutation in this substrain may play a significant role in the pathogenesis of lupus-like autoimmune syndrome.
AB - The autosomal recessive mutant gene, Ipr, has been shown to accelerate the progression of lupus-like autoimmune disease, which is associated with a massive expansion of a unique CD4˜CD8˜ double-negative T cell subset, in MRL/MpJ mice. Here we report a substrain of MRL/MpJ-fpr//pr (MRL-fpr) mice which live almost twice as long with delayed development of glomerulonephritis, compared with conventional MRL-/pr mice. This substrain, termed MRL-/pr.//(//for long-lived), develops generalized lymphadenopathy characteristically seen in MRL-/pr mice. However, the expansion of a double negative Ipr T cell subset is markedly limited with a mean value of 15% in their lymph nodes compared to about 70% in conventional MRL-/pr mice. Overall production of autoantibodies, such as anti-DNA and rheumatoid factors, does not significantly differ between the two MRL-/pr mice. However, serum levels of cryoglobulins, whose major component is lgG3, are markedly diminished in MRL-/pr.//mice with a parallel decrease in lgG3. Since MRL-/pr.//mice still carry the Ipr mutation, as documented by the presence of defects in the Fas antigen, a possible new mutation in this substrain may play a significant role in the pathogenesis of lupus-like autoimmune syndrome.
KW - Autoimmunity
KW - Lymphoproliferation
KW - Mutant mouse
KW - Systemic lupus erythematosus
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U2 - 10.1093/intimm/5.5.525
DO - 10.1093/intimm/5.5.525
M3 - Article
C2 - 8318455
AN - SCOPUS:0027336832
SN - 0953-8178
VL - 5
SP - 525
EP - 532
JO - International Immunology
JF - International Immunology
IS - 5
ER -