Genetic control of the spontaneous activation of CD4+ Th cells in systemic lupus erythematosus-prone (NZB x NZW) F1 mice.
The F(1) hybrid of autoimmune hemolytic anemia-prone NZB and nonautoimmune NZW strains of mice has been studied as a murine model of systemic lupus erythematosus. Both NZB and F(1) hybrid mice show age-dependent spontaneous activation of peripheral CD4(+) T cells as reflected by the elevated frequencies of CD4(+) T cells positive for CD69 early activation marker. Both strains also show age-dependent abnormal decrease of the frequencies of CD62L(+) naive CD4(+) T cells and/or NTA260(+) memory CD4(+) T cells in the spleen. We studied the multigenic control of these abnormal features of peripheral CD4(+) T cells in (NZB x NZW) F(1) x NZW backcross mice by quantitative trait loci mapping and by association rule analysis. The abnormally elevated frequencies of CD69(+)CD4(+) T cells and decreased frequencies of CD62L(+) naive and/or NTA260(+) memory CD4(+) T cells were under the common genetic control, in which the interaction between MHC and a hitherto unknown locus, designated Sta-1 (spontaneous T-cell activation) on chromosome 12, plays a major role. The allelic effects of these loci likely predispose CD4(+) T cells to the loss of self-tolerance, and are responsible for the accelerated autoimmune phenotypes of (NZB x NZW) F(1) hybrid mice.
Fujii
T
T
Department of Biomedical Engineering, Toin Human Science and Technology Center, Toin University of Yokohama, Yokohama, Japan.
Iida
Y
Y
Yomogida
M
M
Ikeda
K
K
Haga
T
T
Jikumaru
Y
Y
Ninami
M
M
Nishimura
N
N
Kodera
Y
Y
Inada
Y
Y
Shirai
T
T
Hirose
S
S
Nishimura
H
H
D000367:Age Factors; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D015551:Autoimmunity / Q000235:genetics*; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005434:Flow Cytometry; D019041:L-Selectin / Q000378:metabolism; D037181:Lectins, C-Type; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology*; D008213:Lymphocyte Activation / Q000235:genetics*; D051379:Mice; D008814:Mice, Inbred NZB; D018895:Microsatellite Repeats / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics; D013154:Spleen / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D000099192:CD69 Antigens
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D019041:L-Selectin; D037181:Lectins, C-Type; D000099192:CD69 Antigens