Rapidly proliferating CD44hiperipheral T cells undergo apoptosis and delay posttransplantation T-cell reconstitution after allogeneic bone marrow transplantation

Autor: Alpdogan, S. Önder, Lu, Sydney X., Patel, Neel, McGoldrick, Suzanne, Suh, David, Budak-Alpdogan, Tulin, Smith, Odette M., Grubin, Jeremy, King, Christopher, Goldberg, Gabrielle L., Hubbard, Vanessa M., Kochman, Adam A., van den Brink, Marcel R.M.
Zdroj: Blood; December 2008, Vol. 112 Issue: 12 p4755-4764, 10p
Abstrakt: Delayed T-cell recovery is an important complication of allogeneic bone marrow transplantation (BMT). We demonstrate in murine models that donor BM-derived T cells display increased apoptosis in recipients of allogeneic BMT with or without GVHD. Although this apoptosis was associated with a loss of Bcl-2 and Bcl-XLexpression, allogeneic recipients of donor BM deficient in Fas-, tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)- or Bax-, or BM-overexpressing Bcl-2 or Akt showed no decrease in apoptosis of peripheral donor-derived T cells. CD44 expression was associated with an increased percentage of BM-derived apoptotic CD4+and CD8+T cells. Transplantation of RAG-2-eGFP–transgenic BM revealed that proliferating eGFPloCD44hidonor BM-derived mature T cells were more likely to undergo to apoptosis than nondivided eGFPhiCD44lorecent thymic emigrants in the periphery. Finally, experiments using carboxyfluorescein succinimidyl ester–labeled T cells adoptively transferred into irradiated syngeneic hosts revealed that rapid spontaneous proliferation (as opposed to slow homeostatic proliferation) and acquisition of a CD44hiphenotype was associated with increased apoptosis in T cells. We conclude that apoptosis of newly generated donor-derived peripheral T cells after an allogeneic BMT contributes to delayed T-cell reconstitution and is associated with CD44 expression and rapid spontaneous proliferation by donor BM-derived T cells.
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