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The Journal of Immunology, 2004, 173: 6654-6659.
Copyright © 2004 by The American Association of Immunologists

Tolerance Induction by Veto CTLs in the TCR Transgenic 2C Mouse Model. I. Relative Reactivity of Different Veto Cells1

Shlomit Reich-Zeliger, Esther Bachar-Lustig, Judith Gan and Yair Reisner2

Department of Immunology, Weizmann Institute of Science, Rehovot, Israel

Several bone marrow cells and lymphocyte subpopulations, known as veto cells, were shown to induce transplantation tolerance across major histocompatibility Ags. Due to the low frequency of the effector T cells against which the veto cells inhibitory activity is aimed, the fate of the effector cells was traditionally followed indirectly by functional limiting dilution assays, which are cumbersome and depend on numerous parameters. In the present study the fate of the effector T cells was monitored directly by FACS, using TCR transgenic mouse CD8+ T cells in which the transgene is directed against H-2d (the 2C model). This assay is validated by demonstrating the potency, selectivity, radiation sensitivity, and contact dependency of anti-third-party CTLs previously demonstrated by the limiting dilution assay. In contrast to veto CTLs, nonactivated CD8+ T cells lack veto activity. Comparison by FACS in the 2C model revealed a hierarchy of veto cells, in the order of veto CTLs activated NK cells, activated CD4+ T cells, and activated B cells. The latter cells as well as nonactivated CD4+ or NK cells were shown to be completely devoid of veto activity.




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S. Reich-Zeliger, E. Bachar-Lustig, A. Bar-Ilan, and Y. Reisner
Tolerance Induction in Presensitized Bone Marrow Recipients by Veto CTLs: Effective Deletion of Host Anti-Donor Memory Effector Cells
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