Naive CD4+ T cell subset is the predominant population involved in cytolysis through Fas-ligand in human at birth.
Here we show that Fas ligand, a death factor that plays a key role in peripheral T cell tolerance and homeostasis, can be induced in peripheral blood mononuclear cells from both newborns (cord) and adults. Indeed, stimulation of both populations by ionomycin and phorbol 12-myristate 13-acetate or through the T cell receptor (anti-CD3) leads to a selective lysis of targets transfected with Fas but not of the parental cell line. This lysis clearly involves a Fas-based mechanism inasmuch as it was correlated with the appearance of Fas ligand transcripts and competitively inhibited by a Fas-Fc fusion protein. Yet, the use of separated T cell populations revealed that both CD4+ and CD8+ T cells express this function in adults whereas the CD4 subset is primarily involved in lysis by a Fas-based mechanism in cord. Altogether these results suggest that distinct T cell subsets might be recruited to exert Fas-based lysis during T cell ontogeny. Furthermore, it is tempting to speculate that CD4+ T cells are primarily involved in peripheral T cell homeostasis and tolerance in early life because they are committed to exert Fas-based lysis before any antigen-priming. Finally, the model of Fas ligand exploration described herein might be of great help for the identification of Fas ligand dysregulation in various diseases in infants, including those patients with autoimmune lymphoproliferative syndrome in which Fas is functional.
Soulimani
N
N
Laboratoire d'Immunologie, Hôpital Robert Debré, Paris, France.
Ansart-Pirenne
H
H
Sibony
O
O
Blot
P
P
Sterkers
G
G
D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007743:Labor, Obstetric; D008562:Membrane Glycoproteins / Q000276:immunology*; D008875:Middle Aged; D011247:Pregnancy; D019014:fas Receptor / Q000276:immunology
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor