HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Reich-Zeliger, S. Articles by Reisner, Y. Search for Related Content PubMed PubMed Citation Articles by Reich-Zeliger, S. Articles by Reisner, Y.

Tolerance Induction in Presensitized Bone Marrow Recipients by Veto CTLs: Effective Deletion of Host Anti-Donor Memory Effector Cells^1,2

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

Veto cells have been defined as cells capable of inducing apoptosis of effector CD8 cells recognizing their disparate MHC Ags. Tolerance induced by donor-type veto cells is desirable, because it is restricted to depletion of anti-donor clones without depletion of other immune specificities. It has been shown that anti-third party CTLs exhibit marked veto activity with reduced capacity to induce graft-vs-host disease, when tested on naive effector cells. However, presensitized T cells could play an important role in graft rejection, and therefore, their sensitivity to veto cells could be critical to the implementation of the latter cells in bone marrow transplantation. To address this question, we compared naive and presensitized TCR transgenic effector CD8 T cells, bearing a TCR against H-2^d. Both cell types exhibited similar predisposition to killing by veto CTLs in vitro, and this killing was dependent in both cell types on Fas-FasL signaling as shown by using Fas-deficient CD8 T cells from (lprx2c) F₁ mice. When tested in a stringent mouse model, in which bone marrow rejection is mediated by adoptively transferred host type T cells into lethally irradiated recipients, veto CTLs were equally effective in overcoming rejection of naive or presensitized host T cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by National Institutes of Health Grant PO1CA100265-01A1, (project 5 of Dana Farber PO1); European Commission LSHB-CT-2004-503319 (Allostem Project); the Gabriella Rich Center for Transplantation Biology Research; and by E. Drake.

² S.R.Z. and E.B.L. contributed to research design and performance and the writing of the paper. A.B. contributed to research design and performance and Y.R. to research design and writing of the paper.

³ Address correspondence and reprint requests to Prof. Yair Reisner, Chairman, Department of Immunology, The Henry H. Drake Professorial Chair of Immunology, Yair Reisner, Weizmann Institute of Science, Department of Immunology, Rehovot, Israel. E-mail address: yair.reisner{at}weizmann.ac.il

⁴ Abbreviations used in this paper: GVHD, graft-vs-host disease.