Host-reactive cytotoxic T lymphocyte precursors in long-lived fully allogeneic mouse bone marrow chimeras.
Fully H-2-incompatible chimeric mice were constructed by grafting lethally (950 rad) irradiated germ-free (GF) CBA (H2k) mice with anti-Thy 1 antibody plus complement-treated allogeneic C57Bl/6 (B6) (H2b) bone marrow cells. These chimeric mice were kept for more than 11 months, either under GF conditions or under barrier-sustained specific-pathogen-free (SPF) conditions. Controls included nonirradiated, nontransplanted, sex- and age-matched CBA and B6 mice raised under SPF conditions, and syngeneic chimeric mice of the CBA----CBA type kept under GF and SPF conditions. All chimeric mice were completely repopulated with donor-type lymphoid cells and showed no clinical or histological evidence of graft-versus-host disease. From the fully allogeneic chimeric mice, we enumerated the numbers of splenic cytotoxic T lymphocyte precursors (CTL-p) that could be clonally expanded under limiting dilution conditions in response to third-party alloantigens, or nonmodified and trinitrophenyl (TNP)-modified stimulator cells bearing host or donor H-2 antigens. The existence of high numbers of alloreactive and host- or donor-type H-2-restricted TNP-specific CTL-p in the spleens of fully allogeneic chimeras indicated almost normal immunocompetence. The surprising finding, however, was that large numbers of host (CBA)-reactive splenic CTL-p were inducible under limiting dilution conditions in healthy long-lived allogeneic chimeras, although these chimeric mice were devoid of any histological or clinical signs of graft-versus-host disease.
D000818:Animals; D001853:Bone Marrow / Q000276:immunology*; D002678:Chimera; D007519:Isoantigens / Q000276:immunology*; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D007519:Isoantigens