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Characterization of donor chimerism, alloreactive host T cells and memory cell development in thymi from mice resistant to neonatal transplantation tolerance.

Certain B10 background mouse strains are resistant to tolerance induction after neonatal inoculation of class I/II MHC-disparate F1 hybrid cells. Despite initial thymic deletion of alloreactive cells, the majority (95%) of these mice reacquire the capacity to reject donor allografts. These current studies examined thymi of adult B10.S (H-2S/H-2E-) mice that neonatally received (B10.S x B10.A)F1 cells, before and after rejection or acceptance of B10.A (H-2k/d/H-2E+) skin grafts. Alloreactive thymic V beta 11+ and V beta 5+ T cells were often reduced in the injected recipients preceding allograft challenge. In some mice a single B10.A skin graft generated an increase in these T cell populations concurrent with allograft rejection. Injected mice that accepted B10.A skin grafts (i.e., tolerant) or that rejected two sequential B10.A grafts often had a reduction of these T cells. Thymic memory cells (CD44high+) were present before transplant in injected mice and reduced in the tolerant mice. Donor chimeric cells were identified in the majority of injected mice before transplant and diminished after B10.A graft application. A greater proportion of chimeric cells coexpressed CD11b or B220 in the tolerant mice. Thus, neonatally injected B10.S mice resistant to tolerance induction reacquire immunocompetent thymic T cells bearing characteristics of memory T cells that could mediate graft rejection. Finally, the initial presentation of chimeric cells (e.g., macrophages) that may efficiently present class I Ags through H-2E likely increases the possibility of adult tolerance.