TY - JOUR
T1 - 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
AU - Broers, Annoek E. C.
AU - Posthumus-van Sluijs, Sandra J.
AU - Spits, Hergen
AU - van der Holt, Bronno
AU - Löwenberg, Bob
AU - Braakman, Eric
AU - Cornelissen, Jan J.
PY - 2003
Y1 - 2003
N2 - 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 received transplants of syngeneic T-cell-depleted (TCD) bone marrow (Ly5.1) with or without supplemented T cells (Ly5.2). IL-7 was administered until day 63 after 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
AB - 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 received transplants of syngeneic T-cell-depleted (TCD) bone marrow (Ly5.1) with or without supplemented T cells (Ly5.2). IL-7 was administered until day 63 after 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
U2 - https://doi.org/10.1182/blood-2002-11-3349
DO - https://doi.org/10.1182/blood-2002-11-3349
M3 - Article
C2 - 12714515
SN - 0006-4971
VL - 102
SP - 1534
EP - 1540
JO - Blood
JF - Blood
IS - 4
ER -