Prevention of autoimmunity and control of recall response to exogenous antigen by Fas death receptor ligand expression on T cells.
Mice with mutations in the gene encoding Fas ligand (FasL) develop lymphoproliferation and systemic autoimmune diseases. However, the cellular subset responsible for the prevention of autoimmunity in FasL-deficient mice remains undetermined. Here, we show that mice with FasL loss on either B or T cells had identical life span as littermates, and both genotypes developed signs of autoimmunity. In addition, we show that T cell-dependent death was vital for the elimination of aberrant T cells and for controlling the numbers of B cells and dendritic cells that dampen autoimmune responses. Furthermore, we show that the loss of FasL on T cells affected the follicular dentritic cell network in the germinal centers, leading to an impaired recall response to exogenous antigen. These results disclose the distinct roles of cellular subsets in FasL-dependent control of autoimmunity and provide further insight into the role of FasL in humoral immunity.
Mabrouk
Imed
I
INSERM U580, Université Paris Descartes, Hopital Necker, 161 rue de Sèvres 75015 Paris, France.
Buart
Stéphanie
S
Hasmim
Meriem
M
Michiels
Christelle
C
Connault
Elizabeth
E
Opolon
Paule
P
Chiocchia
Gilles
G
Lévi-Strauss
Matthieu
M
Chouaib
Salem
S
Karray
Saoussen
S
D000818:Animals; D000941:Antigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D053222:Fas Ligand Protein / Q000235:genetics / Q000276:immunology*; D008206:Lymphatic Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism
D000941:Antigens; D053222:Fas Ligand Protein; C491899:Fas protein, mouse; D019014:fas Receptor