Anti-TCR Vbeta-specific DNA vaccination prolongs heart allograft survival in adult rats.
Allospecific T cells are known to play a central role in the process of allograft rejection. Recently, it has been shown that T cell function could be specifically targeted using DNA vaccination. In our model, PCR analysis of the TCR-beta chain repertoire of T cells infiltrating rejected allografts showed specific expansions of the Vbeta13 and Vbeta2 families. In this study, we tested the effect on allograft survival of DNA vaccination against a specific TCR Vbeta, in a model of heart allograft rejection in adult rats. Our results showed that anti-TCR Vbeta13 DNA vaccination lead to a significant prolongation of allograft survival compared to vaccination against other Vbeta families or untreated recipients. The prolongation of allograft survival correlated in vitro with a decrease in anti-donor reactivity of spleen cells from Vbeta13-vaccinated rats. These results show that, in a transplantation model, DNA vaccination could be used as a method to specifically manipulate a T cell response and thus prolong allograft survival.
Vignes
C
C
INSERM Unité 437, Immunointervention dans les allo-et xeno-transplantations and Institut de Transplantation et de Recherche en Transplantation, Nantes, France.
Chiffoleau
E
E
Brouard
S
S
Douillard
P
P
Coudreuse
D
D
Soulillou
J P
JP
Cuturi
M C
MC
D000818:Animals; D006085:Graft Survival; D016027:Heart Transplantation; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta; D019444:Vaccines, DNA