Evidence that non-deletional mechanisms are responsible for inducing and maintaining unresponsiveness after intrathymic injection of non-professional antigen presenting cells.
BACKGROUND
Intrathymic inoculation of donor alloantigen and concomitant immunosuppressive treatment can induce immune unresponsiveness to alloantigen. To examine the role of non-deletional mechanisms in the development of unresponsiveness, fractionated splenocytes were injected into only 1 lobe of the thymus.


RESULTS
Untreated CBA (H2(k)) mice or controls pre-treated with anti-CD4 monoclonal antibody alone (on Day -28 and -27 relative to transplantation) acutely rejected C57BL/10 (H2(b)) cardiac allografts. Intrathymic inoculation of unfractionated splenocytes, resting B (rB) cells, or dendritic cells into both thymic lobes with the antibody resulted in indefinite survival of cardiac allografts. In contrast, when donor rB cells or dendritic cells were delivered into a single lobe of the thymus with the antibody, only rB cells induced indefinite prolongation of graft survival; unfractionated splenocytes or dendritic cells were markedly less effective. Mice that had 1 of the 2 thymic lobes removed were able to reject grafts even when treated with the antibody 27 days before transplantation. Therefore, T-cell export from 1 thymic lobe was sufficient to induce graft rejection. Finally, adoptive transfer of splenocytes from mice with long-term surviving primary grafts resulting from the intrathymic injection of rB cells significantly prolonged a graft from the same donor strain in a naive syngeneic recipient.


CONCLUSIONS
Taken together, these data suggest that regulatory mechanisms generated by intrathymic injection of a non-professional antigen presenting cell, in this study donor rB cells, suppressed the rejection response mediated by T cells exported from the uninjected lobe.
Niimi
M
M
Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Jones
N D
ND
Morris
P J
PJ
Wood
K J
KJ
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001323:Autoantibodies / Q000008:administration & dosage / Q000276:immunology; D017690:Cell Transplantation; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007267:Injections; D007519:Isoantigens / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D013154:Spleen / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*; D014184:Transplantation, Homologous
D001323:Autoantibodies; D007166:Immunosuppressive Agents; D007519:Isoantigens