Blood Journal
Leading the way in experimental and clinical research in hematology

Murine anti-3rd-party central-memory CD8+ T-cells promote hematopoietic-chimerism under mild conditioning: lymph-node sequestration and deletion of anti-donor T-cells

  1. Eran Ophir1,
  2. Noga Or-Geva1,
  3. Irina Gurevich1,
  4. Orna Tal1,
  5. Yaki Eidelstein1,
  6. Elias Shezen1,
  7. Raanan Margalit1,
  8. Assaf Lask1,
  9. Guy Shakhar1,
  10. David Hagin1,
  11. Esther Bachar-Lustig1,
  12. Shlomit Reich-Zeliger1,
  13. Andreas Beilhack2,
  14. Robert Negrin3, and
  15. Yair Reisner1,*
  1. 1 Department of Immunology, Weizmann Institute of Science, Rehovot, Israel;
  2. 2 Department of Medicine and Interdisciplinary Center for Clinical Research (IZKF), Wuerzburg University, Wuerzburg, Germany;
  3. 3 Divisions of Blood and Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States
  1. * Corresponding author; email: yair.reisner{at}


Transplantation of T-cell-depleted BM (TDBM) under mild conditioning, associated with minimal toxicity and reduced risk of GVHD, offers an attractive therapeutic option for patients with non-malignant hematologic-disorders and can mediate immune tolerance to subsequent organ transplantation. However, overcoming TDBM rejection following reduced-conditioning remains a challenge. Here, we address this barrier using donor-derived central-memory CD8+T-cells (Tcm), directed against 3rd-party antigens. Our results show that fully allogeneic or (hostXdonor)F1-Tcm, support donor chimerism (>6 months) in sublethaly irradiated(5.5Gy) mice, without GVHD symptoms. Chimerism under yet lower irradiation(4.5Gy) was achieved by combining Tcm with short-term administration of low-dose Rapamycin. Importantly, this chimerism resulted in successful donor skin acceptance, while third-party skin was rejected. Tracking of host-anti-donor T-cells (HADTC), that mediate TDBMT rejection, in a novel bioluminescence-imaging model revealed that Tcm both induce accumulation and eradicate HADTC in the LNs, concomitant with their elimination from other organs, including the BM. Further analysis with 2-photon microcopy revealed that Tcm form conjugates with HADTC, resulting in decelerated and confined movement of HADTC within the LNs in an antigen-specific manner. Thus, anti-3rd-party Tcm support TDBMT engraftment under reduced-conditioning through lymph-node sequestration and deletion of HADTC, offering a novel and potentially safe approach for attaining stable hematopoietic chimerism.

  • Submitted July 6, 2012.
  • Accepted November 12, 2012.