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Strategies to enhance T cell reconstitution following severe immunodepletion
Author(s) -
Martinez Mariela Raquel,
Dudakov Jarrod,
Young Lauren,
Brink Marcel
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb150
Subject(s) - homing (biology) , stem cell , t cell , immune system , haematopoiesis , immunology , hematopoietic stem cell transplantation , transplantation , cell therapy , plerixafor , ex vivo , biology , medicine , cancer research , in vivo , microbiology and biotechnology , cxcr4 , chemokine , ecology
Allogeneic hematopoietic stem cell transplant (AHSCT) is one of the only curative therapies for leukemia patients and others with hematological malignancies. Its use is restricted by major complications including post‐transplant immune deficiency which is devastating to the T cell compartment. Promotion of rapid and effective reconstitution of T cell immunity reduces incidence of transplant‐related complications and significantly improves the survival of HSCT recipients. Our previous studies show that precursor T cells (preT) generated ex vivo from stem cells on the OP9‐DL1 culture system can significantly enhance T cell reconstitution in AHSCT recipients. However, despite their regenerative benefits, the homing and seeding of preT to the thymus is relatively inefficient (only 1 out of every 10,000 iv injected preT engraft in the thymus). In the present study we examined strategies to improve the effectiveness of preT treatment. We found that direct administration of lineage‐depleted BM into the thymus can have significant benefit for T cell reconstitution. We also found that small changes in the purification strategy for seeding OP9‐DL1 cultures (based on differential CD150 expression) can have significant impacts on the generation and output of preT. These findings lay the foundation for improving T cell rejuvenation by enhancing the utility of preT as a potential clinical therapy.