Apoptosis of immature thymocytes mediated by E2/CD99.
E2/CD99 is a 32-kDa transmembrane molecule that does not belong to any known family of proteins. It appears to regulate adhesion properties of T cells as previously reported, in particular, the induction of homotypic adhesion in CD4+ CD8+ thymocytes. Apoptosis induced via E2/CD99 displays characteristic morphologic features, but includes early mitochondrial alterations and phosphatidylserine exposure at the outer leaflet of the plasma membrane. It is not followed by detectable DNA fragmentation, and its time course is much longer than apoptosis induced via the Fas/CD95 pathway. It requires 18 h for completion. E2/CD99-induced apoptosis does not require any RNA or protein synthesis and still occurs following blockage of the Fas pathway. It is, however, dependent on CPP32 and IL-1beta-converting enzyme-type cysteine proteases, as shown by blockade with their respective specific inhibitors. This effect is restricted to double-positive thymocytes carrying an intermediate density of CD3 and including all CD69+ cells. Thus, E2/CD99 apears to mediate a distinctive apoptotic signal at a critical stage of thymocyte differentiation, i.e., when positive selection is known to occur.
Bernard
G
G
INSERM Unit 343 Archet Hospital, Nice, France.
Breittmayer
J P
JP
de Matteis
M
M
Trampont
P
P
Hofman
P
P
Senik
A
A
Bernard
A
A
D000071443:12E7 Antigen; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte; D017209:Apoptosis / Q000276:immunology*; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D020170:Caspase 1; D053148:Caspase 3; D020169:Caspases; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology; D002675:Child, Preschool; D003546:Cysteine Endopeptidases / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006801:Humans; D016130:Immunophenotyping; D019169:Jurkat Cells; D037181:Lectins, C-Type; D013601:T-Lymphocytes / Q000276:immunology* / Q000648:ultrastructure; D019014:fas Receptor / Q000502:physiology; D000099192:CD69 Antigens
D000071443:12E7 Antigen; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D020170:Caspase 1; D053148:Caspase 3; D020169:Caspases; D015815:Cell Adhesion Molecules; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors; D037181:Lectins, C-Type; D019014:fas Receptor; D000099192:CD69 Antigens; C061828:CD99 protein, human; C505407:CASP3 protein, human