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IL-7 enhances peripheral T cell reconstitution after allogeneic hematopoietic stem cell transplantation
Önder Alpdogan, … , Barry J. Kappel, Marcel R.M. van den Brink
Önder Alpdogan, … , Barry J. Kappel, Marcel R.M. van den Brink
Published October 1, 2003
Citation Information: J Clin Invest. 2003;112(7):1095-1107. https://doi.org/10.1172/JCI17865.
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IL-7 enhances peripheral T cell reconstitution after allogeneic hematopoietic stem cell transplantation

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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.

Authors

Önder Alpdogan, Stephanie J. Muriglan, Jeffrey M. Eng, Lucy M. Willis, Andrew S. Greenberg, Barry J. Kappel, Marcel R.M. van den Brink

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Figure 4

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Most de novo–generated T cells after allogeneic BMT with purified hemato...
Most de novo–generated T cells after allogeneic BMT with purified hematopoietic stem cells have a memory/activated phenotype. Lethally irradiated (1,300 cGy) CBA/J mice were transplanted with either B10.BR TCD-BM (allogeneic BMT) or lineage-negative SCA-1+c-kit+ B10.BR BM cells (2 × 104). IL-7 (10 μg/day) or PBS (control) was administered by intraperitoneal injection from day 21 to day 28 after allogeneic BMT, and from day 28 to day 35 after allogeneic SCT. Animals were sacrificed and harvested on day 28 (BMT) and day 35 (SCT). Absolute numbers of specific donor-derived cell populations were calculated from total cell counts and percentages of T cells by flow cytometric analysis. Naive CD4+ T cells were defined as CD44lowCD62Lhigh, activated CD4+ T cells as CD44highCD62Lhigh, memory CD4+ T cells as CD44highCD62Llow, naive CD8+ T cells as CD44low, and memory/activated CD8+ T cells as CD44high. Values represent the mean cell number ± SEM (SCT: n = 3; BMT: n = 16).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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