T cell repertoire alterations of vascularized xenografts.
The role of T cells in the rejection of vascularized xenografts has been little explored. Because of the high potential diversity of xenoantigens, it has been suggested that xenotransplantation could induce a strong cellular response that could contribute to delayed rejection. Alternatively, alterations in molecular interactions could impair the T cell response. Because the analysis of TCR repertoire in vivo indirectly reflects the nature and the magnitude of T cell xenorecognition, we took advantage of the possibility of obtaining long term survival of hamster heart xenografts in rat recipients treated with a combination of cobra venom factor and cyclosporin A (CsA), to analyze T cell infiltration and, for the first time, V beta TCR usage, at the complementarity-determining region 3 level, in accommodated and rejected xenografts, compared with allografts. After withdrawal of CsA (on day 40), the analysis of V beta family expression and corresponding complementarity-determining region 3 lengths in rejected xenografts revealed a Gaussian pattern, in contrast to a much more restricted pattern in rejected allografts (p = 0.002), suggesting that, after withdrawal of CsA, all the underrepresented T cell clones are rapidly expanded in xenografts. These results correlate with the rapid kinetics of rejection (4 +/- 1 days), the high number of T cells, the rapid expression of markers of activation (IL-2 receptor alpha-chain and class II receptor), and the strong deposit of IgG Abs in rejected xenografts. Taken together, these results suggest that the intensity and diversity of the T cell response to xenografts could be stronger than the response to allografts in vivo.
Brouard
S
S
Institut National de la Santé et de la Recherche Médicale (INSERM)-Unité 437, Nantes, France.
Vanhove
B
B
Gagne
K
K
Neumann
A
A
Douillard
P
P
Moreau
A
A
Cuturi
C
C
Soulillou
J P
JP
D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D006224:Cricetinae; D016572:Cyclosporine / Q000627:therapeutic use; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D016027:Heart Transplantation / Q000276:immunology / Q000473:pathology; D007136:Immunoglobulins / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008647:Mesocricetus; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D014183:Transplantation, Heterologous / Q000276:immunology* / Q000473:pathology; D014184:Transplantation, Homologous
D007136:Immunoglobulins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016572:Cyclosporine