Evidence that I-E-negative mice resistant toneonatal H-2 tolerance induction display ubiquitous thymic clonal deletion of donor-reactive T cells

Phillip Ruiz, J. Wayne Streilein

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

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 Vβ11+ cells in the immediate postnatal period. To test this possibility, we have examined Vβ11 expression and tolerogen-responsiveness among T cells of thymus and spleens harvested periodically from B10.S mice after neonatal inoculation of (B10.A x B10.S) F1 cells. We found that Vβ11+ 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 Vβ11+ 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 Vβ11+ 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.

Original languageEnglish (US)
Pages (from-to)321-328
Number of pages8
JournalTransplantation
Volume55
Issue number2
DOIs
StatePublished - Feb 1993

ASJC Scopus subject areas

  • Transplantation

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