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.
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.
Broers
Annoek E C
AE
Department of Hematology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
Posthumus-van Sluijs
Sandra J
SJ
Spits
Hergen
H
van der Holt
Bronno
B
Löwenberg
Bob
B
Braakman
Eric
E
Cornelissen
Jan J
JJ
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000379:methods*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D016654:Genes, RAG-1 / Q000235:genetics; D015851:Interleukin-7 / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
D015851:Interleukin-7; D011994:Recombinant Proteins