Rapidly proliferating CD44hi peripheral T cells undergo apoptosis and delay posttransplantation T-cell reconstitution after allogeneic bone marrow transplantation Journal Article
| Authors: | Alpdogan, S. O.; Lu, S. X.; Patel, N.; McGoldrick, S.; Suh, D.; Budak-Alpdogan, T.; Smith, O. M.; Grubin, J.; King, C.; Goldberg, G. L.; Hubbard, V. M.; Kochman, A. A.; van den Brink, M. R. M. |
| Article Title: | Rapidly proliferating CD44hi peripheral T cells undergo apoptosis and delay posttransplantation T-cell reconstitution after allogeneic bone marrow transplantation |
| Abstract: | 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-XL expression, 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 eGFPloCD44hi donor BM-derived mature T cells were more likely to undergo to apoptosis than nondivided eGFPhiCD44lo recent 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 CD44 hi phenotype 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. © 2008 by The American Society of Hematology. |
| Keywords: | protein kinase b; controlled study; protein expression; transplantation, homologous; unclassified drug; genetics; nonhuman; cd8 antigen; antigen expression; cd8+ t lymphocyte; cell proliferation; lymphocyte proliferation; t lymphocyte; t-lymphocytes; animal cell; mouse; animal; cytology; metabolism; animals; mice; cells, cultured; gene overexpression; protein bcl 2; apoptosis; cell maturation; fas antigen; green fluorescent protein; animal experiment; allogenic bone marrow transplantation; cell differentiation; pathology; protein bcl xl; mice, inbred balb c; mice, inbred c57bl; physiology; time; time factors; transgenic mouse; c57bl mouse; mice, transgenic; immunology; donor; bagg albino mouse; cell culture; thymus; tumor necrosis factor related apoptosis inducing ligand; cd4+ t lymphocyte; graft versus host reaction; adoptive transfer; immunomodulation; cd4 antigen; immune deficiency; rag2 protein; hermes antigen; homeostasis; bone marrow transplantation; graft vs host disease; graft recipient; allotransplantation; cell labeling; transgenics; tnf-related apoptosis-inducing ligand; protein bax; tnfsf10 protein, mouse; antigens, cd44; bcl-2-associated x protein; antigens, cd95; isograft |
| Journal Title: | Blood |
| Volume: | 112 |
| Issue: | 12 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2008-12-01 |
| Start Page: | 4755 |
| End Page: | 4764 |
| Language: | English |
| DOI: | 10.1182/blood-2008-02-142737 |
| PUBMED: | 18815289 |
| PROVIDER: | scopus |
| PMCID: | PMC2597141 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 4" - "Export Date: 17 November 2011" - "CODEN: BLOOA" - "Source: Scopus" |
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