Intrathymic administration of B cells induces prolonged survival of fully allogeneic cardiac grafts without prolonged deletion of donor-specific thymocytes.
Intrathymic (IT) injection of alloantigen has been shown to induce unresponsiveness to allografts although the exact mechanisms of tolerance induction remains unclear. C57BL/10 (H2b) cardiac allografts were accepted in C3H/He (H2k) mice pretreated with IT inoculation of donor splenocytes (1 x 10(6)) in combination with a depleting anti-CD4 monoclonal antibody 27 days before cardiac transplantation. To investigate which cell types were responsible for tolerance induction by IT injection of alloantigen, resting B (rB) cells or dendritic cells were used as the thymic inoculum instead of whole splenocytes. IT injection of rB cells induced indefinite graft prolongation in all recipients while only 20% of mice that had received IT injection of dendritic cells accepted grafts for over 100 days. In contrast, IT injection of dendritic cells resulted in significant deletion of donor-specific thymocytes whereas rB cells were relatively ineffective. IT deletion is not essential for the induction of tolerance by IT injection of rB cells; nondeletional mechanisms can be involved.
Niimi
M
M
Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Headington, UK.
Jones
N D
ND
Pajaro
O B
OB
Morris
P J
PJ
Wood
K J
KJ
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013950:Thymus Gland; D013997:Time Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous