T-cell-mediated rejection of vascularized xenografts in the absence of induced anti-donor antibody response.
T cells are considered to play a major indirect role in the pathogenesis of xenograft vascular rejection, by promoting the induction of anti-donor antibodies that trigger complement- and antibody-dependent cell cytotoxicity. However, how vigorous the T cell xenoresponse is in vivo, and whether, besides their helper function, T cells are capable of directly affecting the graft is still unclear. We have previously shown that cyclosporine A (CsA) withdrawal in accommodated cardiac xenograft recipient allows for a rapid and dense T-cell infiltration, concomitant to an acute graft rejection. In this paper we further characterize the role of T cells in this rejection process and we demonstrate that adoptive transfer of CD4+ T cells in irradiated recipients of long-term cardiac xenografts is sufficient to trigger acute rejection, in the absence of any detectable induced anti-hamster antibody response. Therefore, our data suggest that unusually strong T-cell response will be another major barrier to xenotransplantation, even if antibody-mediated vascular rejection is controlled.
Sebille
F
F
Institut National de la Santé et de la Recherche Médicale-Unit 437, Immunointervention dans les Allo-et les Xénotransplantations and Institut de Transplantation Et de Recherche en Transplantation, Nantes, France.
Guillet
M
M
Brouard
S
S
Gagne
K
K
Petzold
T
T
Blancho
G
G
Vanhove
B
B
Soulillou
J P
JP
D019264:Adoptive Transfer; D000818:Animals; D000910:Antibodies, Heterophile / Q000097:blood*; D006224:Cricetinae; D016207:Cytokines / Q000235:genetics; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008647:Mesocricetus; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D013997:Time Factors; D014158:Transcription, Genetic; D014183:Transplantation, Heterologous / Q000276:immunology*
D000910:Antibodies, Heterophile; D016207:Cytokines; D007166:Immunosuppressive Agents