Fas ligand, tumor necrosis factor-alpha expression, and apoptosis during allograft rejection and tolerance.
BACKGROUND
Cytotoxic T cells can induce target cell lysis and apoptosis by different pathways. The interactions of CD95 antigen (Fas) with its ligand (CD95L) and of tumor necrosis factor (TNF)-alpha with its receptor (TNF-R1) lead to apoptotic cell death. Recently, conflicting studies have been published concerning the expression and the role of CD95L in allograft rejection and tolerance.


METHODS
In this study, the intragraft expression of CD95/CD95L and TNF-alpha and the frequency and distribution of apoptotic cells were compared in a model of heterotopic cardiac allograft in the rat in which recipients were either not treated (acute rejection) or pretreated with donor-specific blood transfusion (tolerant).


RESULTS
In the acutely rejected allografts, a peak in the expression of CD95L and TNF-alpha and in the number of apoptotic cells was observed during the first week after transplantation; apoptotic cells were confined to graft-infiltrating cells. In the tolerated allografts, however, levels of graft-infiltrating cell apoptosis and CD95L and TNF-alpha expression during the same period of time were dramatically lower. The expression of Fas was constitutive and was not modulated during acute rejection or tolerance.


CONCLUSIONS
This down-regulation of CD95L and TNF-alpha in allografts rendered tolerant by donor-specific transfusion suggests a role for apoptosis-inducing pathways in acute allograft rejection.
Josien
R
R
INSERM U437 Immunointervention dans les Allo et Xénotransplantations, Nantes, France.
Müschen
M
M
Gilbert
E
E
Douillard
P
P
Heslan
J M
JM
Soulillou
J P
JP
Cuturi
M C
MC
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001803:Blood Transfusion; D053222:Fas Ligand Protein; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D016027:Heart Transplantation; D007108:Immune Tolerance / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D014019:Tissue Donors; D016042:Transplantation, Heterotopic; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D019014:fas Receptor / Q000032:analysis
D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor