Influence of a small number of mature T cells in donor bone marrow inocula on reconstitution of lymphoid tissues and negative selection of a T cell repertoire in the recipient.
Allo-chimerism and clonal elimination of self antigen (Ag) (Ia + Mls-1a) reactive V beta 6+ T cells were analyzed and compared between allogeneic bone marrow (BM) chimeras reconstituted with BM cells which had been treated with anti-Thy-1 monoclonal antibody (mAb) plus complement (C) (T- chimeras) and BM chimeras which had been reconstituted with BM cells pretreated with anti-Thy-1 mAb alone (T+ chimeras). When lethally irradiated AKR (Mls-1a) mice were reconstituted with BM cells from B10 or B10 H-2 congenic mice, both T+ and T- chimeras were entirely free of signs of graft-versus-host reaction (GVHR). However, complete replacement of the AKR lymphoid tissues by donor BM cells was accomplished at an early stage in T+ chimeras but not in T- chimeras. On the other hand, clonal elimination of V beta 6+ T cells reactive to the recipient Ag (Mls-1a) was abolished in T+ chimeras but successfully induced in T- chimeras. The V beta 6+ T cells not eliminated in T+ chimeras showed depressed responses against Mls-1a antigens. The findings herein demonstrate that T cells which contaminate a BM inoculum survive in recipient mice after treatment with anti-Thy-1 mAb without C in vitro followed by BMT. The surviving T cells have been estimated to represent fewer than 0.5% of the BM cells inoculated. These cells appear to accelerate the full replacement of recipient lymphoid tissues by donor cells. Furthermore, the T cells which survive in the marrow inoculum influence eventually the development of a tolerant state in the T cell repertoire of the donor.
Arase-Fukushi
N
N
Institute of Immunological Science, School of Medicine, Hokkaido University, Japan.
Arase
H
H
Wang
B
B
Hirano
M
M
Ogasawara
K
K
Good
R A
RA
Onoé
K
K
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D006087:Graft vs Host Reaction / Q000276:immunology*; D007108:Immune Tolerance / Q000502:physiology; D008221:Lymphoid Tissue / Q000166:cytology*; D051379:Mice; D008806:Mice, Inbred AKR; D008815:Mice, Inbred Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013601:T-Lymphocytes / Q000276:immunology*; D018183:Transplantation Chimera / Q000276:immunology*; D014916:Whole-Body Irradiation
D016693:Receptors, Antigen, T-Cell, alpha-beta