Effects of Thy-1+ cell depletion on the capacity of donor lymphoid cells to induce tolerance across an entire MHC disparity in sublethally irradiated adult hosts.
Thy-1+ cell depletion with anti-Thy-1.2 mAb and complement markedly reduced the capacity of C57BL/6J, H-2b bone marrow to establish mixed lymphoid chimerism and induce tolerance to C57BL/6J skin grafts across an entire MHC disparity in BALB/c, H-2d hosts conditioned with sublethal, fractionated 7.5 Gy total-body irradiation. In this model tolerance can be transferred to secondary irradiated BALB/c hosts only by cells of C57BL/6J donor, not host, genotype isolated from the spleens of tolerant hosts. Thy-1+ cell depletion abolished the capacity of C57BL/6J donor cells from tolerant BALB/c host spleens to transfer tolerance. The capacity of semiallogeneic BALB/c x C57BL/6J F1, H-2d/b donor BM and spleen cells to induce chimerism and tolerance to C57BL/6J skin grafts in BALB/c parental hosts was also reduced by Thy-1+ cell depletion. Thus the requirement for donor Thy-1+ cells cannot be explained simply on the basis of alloaggression. It is unlikely that the requisite Thy-1+ cells are nonspecific suppressor cells: Thy-1+ cell depletion had no effect on the slight but significant prolongation of third-party C3H/HeJ, H-2k skin grafts in irradiated BALB/c hosts injected with allogeneic C57BL/6J or semiallogeneic BALB/c x C57BL/6J F1 BM compared to irradiated controls injected with medium only. Furthermore, injections of semiallogeneic F1 spleen cells had no significant effect on the survival of the third-party grafts, although these cells were fully capable of inducing tolerance, and their capacity to induce tolerance was significantly reduced by Thy-1+ cell depletion. The requirement for a specific population of lymphoid cells, i.e. Thy-1+, remains unexplained but suggests that donor cells might play a role in the induction or maintenance of tolerance in this model other than merely providing a circulating source of donor antigens.
Pierce
G E
GE
University of Kansas College of Health Sciences, Kansas City 66103.
Watts
L M
LM
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis*; D016026:Bone Marrow Transplantation; D006183:H-2 Antigens / Q000276:immunology*; D007108:Immune Tolerance; D007116:Immunization, Passive; D007165:Immunosuppression Therapy / Q000379:methods*; D008285:Major Histocompatibility Complex; D051379:Mice; D008815:Mice, Inbred Strains; D011828:Radiation Chimera; D016038:Skin Transplantation; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*; D018800:Thy-1 Antigens; D014916:Whole-Body Irradiation
D000954:Antigens, Surface; D006183:H-2 Antigens; D018800:Thy-1 Antigens