Acute graft-versus-host reaction in SCID mice leads to an abnormal expansion of CD8+ V beta 14+ and a broad inactivation of donor T cells followed by a host-restricted tolerance and a normalization of the TCR V beta repertoire in the chronic phase.
The persistence and selection of allogeneic CBA/J T lymphocytes were studied during graft-versus-host (GvH) reaction in immunodeficient C.B-17 SCID (SCID) mice. After neonatal injection the donor cells primarily migrated to the spleen plus lymph nodes (SL) and the thymus of the recipients. Thirteen days post engraftment, CD8+ cells in SL had increased five times in cell number with an 18-fold increase of CD8+ V beta 14+ cells, paralleled by clinical signs of GvH disease (GvHD). Donor lymphocytes from these mice were proliferative unresponsive to allogeneic Balb/c or C57Bl/6 SL cells, whereas 8 weeks post injection the tolerance was confined to H-2d specific donor cells. Here, spleens had a total cell content similar to untreated SCID mice but the average percentage of donor cells had reached 25%. Moreover, the CD4/CD8 cell ratio in the donor population in SL and thymus had changed to normal and the TCR V beta repertoire was similar to that of the originally injected cells. Following secondary transfer into syngeneic CBA/Ca nu/nu recipients donor cells regained a significant but reduced response to H-2d stimulators indicating that the antigen specific tolerance of allogeneic donor cells in the SCID mice was due, at least in part, to a reversible state of anergy.
Schneider
M K
MK
National Veterinary Institute, Laboratory for Vaccine Research, Uppsala, Sweden.
Grönvik
K O
KO
D000208:Acute Disease; D000818:Animals; D016516:CD4-CD8 Ratio; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D005434:Flow Cytometry; D006087:Graft vs Host Reaction / Q000276:immunology*; D007108:Immune Tolerance; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D016513:Mice, SCID; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D016511:Severe Combined Immunodeficiency / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta