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Prepublished online as a Blood First Edition Paper on April 24, 2003; DOI 10.1182/blood-2002-11-3349.
Submitted November 6, 2002
Accepted April 7, 2003
Interleukin-7 improves T-cell recovery after experimental T-cell-depleted bone marrow transplantation in T-cell-deficient mice by strong expansion of recent thymic emigrants
Annoek E C Broers, Sandra J Posthumus-van Sluijs, Hergen Spits, Bronno van der Holt, Bob Loewenberg, Eric Braakman, and Jan J Cornelissen*
Department of Hematology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
Department of Immunology, Dutch Cancer Institute, Amsterdam, The Netherlands
Department of Statistics, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
* Corresponding author; email: j.cornelissen{at}erasmusmc.nl.
Interleukin-7 (IL-7) has been shown to enhance thymic output of newly developed T-cells following bone marrow transplantation (BMT) in mice. In addition, IL-7 may affect peripheral expansion of T-cells. In order to study the relative contribution of thymopoiesis versus peripheral T-cell expansion in the setting of compromised thymopoiesis, we have applied IL-7 in an experimental stem cell transplantation model using T-cell deficient RAG-1-/- mice. C57BL/6 RAG-1-/- mice were transplanted with syngeneic T-cell depleted (TCD) bone marrow (Ly5.1) with or without supplemented T-cells (Ly5.2). IL-7 was administered until day 63 post-BMT. Peripheral blood T- and B-cell recovery was quantified by flow cytometry and thymopoiesis was studied by quantification of T-cell receptor rearrangement excision circles (TRECs). In mice receiving a T-cell replete BMT, IL-7 selectively expanded mature CD45.2+T-cells, without affecting the recovery of new bone marrow derived CD45.1+ T-cells. In contrast, IL-7 significantly enhanced the recovery of bone marrow derived T-cells after TCD-BMT. Quantification of TRECs in mice receiving a TCD-BMT revealed that enhanced T-cell recovery following IL-7 treatment resulted from a strong expansion of newly developed naive T-cells. These results suggest that peripheral expansion of recent thymic emigrants or mature T-cells may be a preferential mechanism by which IL-7 enhances T-cell recovery after BMT.
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