Soluble Fas ligand-susceptible "memory" cells in mice but not in human: potential role of soluble Fas ligand in deletion of auto-reactive cells.
Human soluble Fas ligand (sFasL) has an apoptotic activity in contrast to murine sFasL. The physiological function of human sFasL is not known, while the pathological consequence of sFasL overproduction has been reported. To understand the physiological function of (human) sFasL, murine and human lymphocytes were treated with sFasL. sFasL treatment significantly decreased CD45RBlo "memory" CD4+ lymphocyte fraction and increased propidium iodide (PI)+ apoptotic CD45RBloCD4+ lymphocytes among murine peripheral lymphocytes. However, sFasL treatment neither decreased CD45RO+ "memory" CD4+ lymphocyte fraction nor increased PI+ CD45RO+CD4+ lymphocytes among human peripheral lymphocytes, suggesting that the deletion of memory cells by sFasL had already occurred in vivo. Patients with systemic lupus erythematosus had sFasL-susceptible "memory" cell fraction suggesting an incomplete deletion of such "memory" cells. These results suggest that the physiological function of human sFasL is to delete the potentially auto-reactive "memory" lymphocytes, which complements membrane FasL (mFasL)-mediated deletion of auto-reactive cells in human beings but not in mice.
Kim
Sunshin
S
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Ki
Ja Young
JY
Lee
Tae H
TH
Suk
Kyungho
K
Cha
Hoon-Suk
HS
Koh
Eun-Mi
EM
Yagita
Hideo
H
Lee
Myung-Shik
MS
D000818:Animals; D017209:Apoptosis; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D017637:Clonal Deletion; D003602:Cytotoxicity, Immunologic; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D053222:Fas Ligand Protein; D006801:Humans; D007156:Immunologic Memory; D066298:In Vitro Techniques; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D016688:Mice, Inbred NOD; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D012995:Solubility; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1