expansion of recent thymic emigrants bone marrow transplantation in T-cell-deficient mice by strong Interleukin-7 improves T-cell recovery after experimental T-cell-depleted

ABSTRACTInterleukin-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.From bloodjournal.hematologylibrary.org by guest on May 30, 2013. For personal use only.