Adoptive transfer of transplantation tolerance mediated by CD4+CD25+ and CD8+CD28- regulatory T cells induced by anti-donor-specific T-cell vaccination.
Previous studies have shown that vaccinating rodents with anti-donor-specific T cells significantly prolonged allograft survival; however, the putative mechanism of the tolerance remains unclear. In this study, we used the model of heterotopic heart transplantation between the C57BL/6 donor mice and BALB/c recipient mice vaccinated with anti-donor (C57BL/6) or anti-third party (C3H)-specific T cells to determine whether T cells prolong survival of mouse heart allografts and which cells were involved in induction of allograft tolerance. We observed that the mean survival time (MST) of C57BL/6 heart grafts in BALB/c mice vaccinated with anti-C57BL/6 specific T cells (43.1 +/- 4.7 days) was prolonged from that in untreated BALB/c mice (9.5 +/- 1.1 days) or BALB/c mice receiving anti-C3H-specific T cells (10.4 +/- 1.9 days). These results suggested that alloantigen-specific T-cell vaccination significantly prolonged cardiac allograft survival. The CD4+CD25+ or CD8+CD28- T cells purified from splenocytes of BALB/c mice vaccinated with anti-donor-specific T cells proliferated markedly in response to irradiated anti-C57BL/6-specific T cells in vitro. Adoptive transfer of these CD4+CD25+ or CD8+CD28- T cells to naïve syngenic mice significantly prolonged the survival of heart allografts. These data suggested that anti-donor-specific T-cell vaccination induced development of CD4+CD25+ or CD8+CD28- regulatory T cells, which in turn mediated allogeneic-specific tolerance.
Wang
J
J
Laboratory of Immunology, 454th Hospital of PLA, Nanjing, China.
Zhang
L
L
Tang
J
J
Jiang
S
S
Wang
X
X
D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D018106:CD28 Antigens / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology*; D017690:Cell Transplantation / Q000379:methods; D005260:Female; D016027:Heart Transplantation / Q000276:immunology*; D007114:Immunization / Q000379:methods; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation*; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology
D018106:CD28 Antigens; D015704:CD4 Antigens; D016827:CD8 Antigens; D053645:Interleukin-2 Receptor alpha Subunit