Evidence that I-E-negative mice resistant to neonatal H-2 tolerance induction display ubiquitous thymic clonal deletion of donor-reactive T cells.
Induction of neonatal H-2 tolerance is highly efficient in most allodisparate strain combinations, with the exception of those in which neonatal recipients do not, but donor cells do, express I-E molecules. For example, less than 25% of I-E-nonexpressing B10.S mice become tolerant following neonatal injection with I-E+ (B10.AxB10.S)F1 cells. It has been hypothesized that the high rate of nontolerance observed in I-E-nonexpressing neonatal recipients of injections of I-E-bearing cells is caused by a failure to delete V beta 11+ cells in the immediate postnatal period. To test this possibility, we have examined V beta 11 expression and tolerogen-responsiveness among T cells of thymus and spleens harvested periodically from B10.S mice after neonatal inoculation of (B10.AxB10.S) F1 cells. We found that V beta 11+ cells were selectively eliminated within 1-2 days from the thymus glands of all recipient mice, B10.A-specific proliferative T cells disappeared concordantly, and the thymus glands contained donor-derived chimeric cells. Subsequently, an increasing proportion of injected mice acquired V beta 11+ thymocytes and B10.A-responsive T cells, while losing chimeric cells. However, deletion and in vitro nonreactivity were still apparent in the majority of mice at 60 days of age. We conclude that neonatal inoculation of I-E-expressing cells established thymic chimerism and caused profound elimination of V beta 11+ cells from the thymus glands of all injected mice. Therefore, the failure of the majority of neonatally injected B10.S mice to display transplantation tolerance of B10.A antigens as adults cannot be ascribed to an inability to delete I-E-reactive thymocytes.
Ruiz
P
P
Department of Pathology, University of Miami School of Medicine, Florida 33101.
Streilein
J W
JW
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology*; D006410:Hematopoiesis; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta