Abstract: |
We used clinically relevant murine allogeneic bone marrow transplantation (BMT) models to study the mechanisms by which IL-7 administration can improve posttransplant peripheral T cell reconstitution. After transplant we could distinguish two populations of mature donor T cells: (a) alloreactive T cells with decreased expression of CD127 (IL-7 receptor α chain) and (b) nonalloreactive T cells, which express CD127 and undergo homeostatic proliferation. IL-7 administration increased the homeostatic proliferation of nonalloreactive T cells, but had no effect on alloreactive T cells and the development of graft-versus-host disease. Allogeneic transplant of purified hematopoietic stem cells and adoptive transfer of thymocytes into lethally irradiated hosts suggested that recent thymic emigrants can undergo homeostatic proliferation and acquire a memory-like phenotype. We found by BrdU pulse-chase, cell cycle, and annexin V analyses that IL-7 administration has significant proliferative and antiapoptotic effects on posttransplant peripheral T cells. We conclude that homeostatic expansion is important for T cell reconstitution after allogeneic BMT and involves both transferred mature T cells and recent thymic emigrants. Apart from its thymopoietic effects, IL-7 promotes peripheral T cell reconstitution through its selective proliferative and antiapoptotic effects on nonalloreactive and de novo-generated T cells, but has no effect on alloreactive T cells. |
Keywords: |
controlled study; transplantation, homologous; mortality; nonhuman; flow cytometry; cell proliferation; lymphocyte proliferation; t lymphocyte; t-lymphocytes; animal cell; mouse; animal; animals; mice; interleukin 7; animal model; stem cell transplantation; hematopoietic stem cell transplantation; drug effect; mice, inbred c57bl; c57bl mouse; t lymphocyte receptor; immunology; graft versus host reaction; hematopoietic stem cell; cba mouse; mice, inbred cba; hermes antigen; memory cell; homeostasis; bone marrow transplantation; graft vs host disease; thymocyte; immunologic memory; allotransplantation; interleukin-7; receptors, interleukin-7; spleen cell; immunological memory; interleukin 2 receptor; receptors, interleukin-2; antigens, cd44; interleukin 7 receptor; female; priority journal; article
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