TY - JOUR
T1 - Functional significance of the Fas molecule in naive lymphocytes
AU - Senju, Satoru
AU - Negishi, Izumi
AU - Motoyama, Noboru
AU - Wang, Fanping
AU - Nakayama, Kei Ichi
AU - Nakayama, Keiko
AU - Lucas, Philip J.
AU - Hatakeyama, Shigetsugu
AU - Zhang, Qing
AU - Yonehara, Shin
AU - Loh, Dennis Y.
N1 - Funding Information:
We thank Dr S Nagata for the mouse Fas cDNA clone pMF1, and Drs I. T Chan, J D Alvarez and L. B Dustin for helpful discussions This work was supported by the Japan Society for the Promotion of Science (N. M ), the Harold Simmons Leukemia Fund (P J. L ) and the Howard Hughes Medical Institute (D. Y L).
PY - 1996
Y1 - 1996
N2 - The Fas molecule mediates apoptotic signal in many cell types. Mouse mutations (Ipr, Ipr(cg), gld), which impair the function of Fas, cause spontaneous autoimmune disease. We generated Fas-deficient (Fas(-/-)) mice by homologous recombination. In embryonic stem cells Fas(-/-) mice developed Ipr-like disease, confirming that the abnormality of Fas is causal in the Ipr phenotype. We also made Fas(-/-) chimeric mice composed of a mixture of Fas(+/+) and Fas(-/-) cells. The chimeric mice also showed the Ipr phenotype. In Fas(-/-) chimeric mice, the Fas-deficient population expanded progressively among mature T and a lymphocytes. The expansion of Fas-deficient lymphocytes occurred at the naive, pre-primed, lymphocyte stage. These results suggest that the Fas molecule functions not only after antigenic stimulation, as previously hypothesized, but also at the naive lymphocyte stage.
AB - The Fas molecule mediates apoptotic signal in many cell types. Mouse mutations (Ipr, Ipr(cg), gld), which impair the function of Fas, cause spontaneous autoimmune disease. We generated Fas-deficient (Fas(-/-)) mice by homologous recombination. In embryonic stem cells Fas(-/-) mice developed Ipr-like disease, confirming that the abnormality of Fas is causal in the Ipr phenotype. We also made Fas(-/-) chimeric mice composed of a mixture of Fas(+/+) and Fas(-/-) cells. The chimeric mice also showed the Ipr phenotype. In Fas(-/-) chimeric mice, the Fas-deficient population expanded progressively among mature T and a lymphocytes. The expansion of Fas-deficient lymphocytes occurred at the naive, pre-primed, lymphocyte stage. These results suggest that the Fas molecule functions not only after antigenic stimulation, as previously hypothesized, but also at the naive lymphocyte stage.
UR - https://www.scopus.com/pages/publications/9044248951
UR - https://www.scopus.com/pages/publications/9044248951#tab=citedBy
U2 - 10.1093/intimm/8.3.423
DO - 10.1093/intimm/8.3.423
M3 - Article
C2 - 8671629
AN - SCOPUS:9044248951
SN - 0953-8178
VL - 8
SP - 423
EP - 431
JO - International immunology
JF - International immunology
IS - 3
ER -