Studies of immunologic tolerance to host minor histocompatibility antigens following allogeneic bone marrow transplantation in mice.
We showed previously that transplantation of 10(7) unmanipulated C57BL/6 marrow cells to irradiated LP mice yields healthy (B6-LP) chimeras showing no signs of rejection or graft-versus-host disease (GVHD). The aim of this work was to gain more insight into the mechanism(s) responsible for tolerance to host minor histocompatibility antigens following allogeneic bone marrow transplantation (BMT). (B6-LP) chimeras showed very good immune reconstitution when studied in vitro for proliferative response to mitogens and alloantigens and generation of T cell cytotoxic activity. In co-culture experiments their spleen cells showed no natural suppressor activity. When used as cell donors, their capacity to initiate GVHD in four strains of mice presenting H-2 differences was normal when compared to C57BL/6 donors. However, they provoked no GVHD in the three strains of H-2 compatible mice studied. Re-irradiated (B6-LP) chimeras rapidly died of GVHD following injection of C57BL/6 marrow + spleen cells. (B6-LP.R111) chimera cells appeared tolerant to LP minor antigens presented in the context of H-2r or H-2b. No anamnestic anti-idiotypic suppressor response was noted when stable (B6-LP) chimeras were stimulated with naive C57BL/6 cells. These findings suggest that in BMT chimeras transplanted across minor histocompatibility barriers: (1) both host and donor-derived antigen-presenting cells can present host antigens to donor T cells whose numbers in the marrow inoculum will determine if GVHD or tolerance will ensue, (2) GVHD can be triggered by only a limited number of 'dominant' minor antigens, and (3) we found no evidence for the presence of natural suppressors, veto cells or anti-idiotypic suppressor T cells.
Perreault
C
C
Department of Hematology, Maisonneuve-Rosemont Hospital, Montreal, Canada.
Allard
A
A
Brochu
S
S
Poupart
C
C
Fontaine
P
P
Bélanger
R
R
Gyger
M
M
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D006086:Graft vs Host Disease / Q000209:etiology; D007108:Immune Tolerance; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D015778:Minor Histocompatibility Antigens; D011828:Radiation Chimera / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014184:Transplantation, Homologous
D015778:Minor Histocompatibility Antigens