IL-7 enhances peripheral T cell reconstitution after allogeneic hematopoietic stem cell transplantation.
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 alpha 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.
Alpdogan
Onder
O
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Muriglan
Stephanie J
SJ
Eng
Jeffrey M
JM
Willis
Lucy M
LM
Greenberg
Andrew S
AS
Kappel
Barry J
BJ
van den Brink
Marcel R M
MR
D000818:Animals; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation; D006706:Homeostasis; D018960:Hyaluronan Receptors / Q000032:analysis; D007156:Immunologic Memory; D015851:Interleukin-7 / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D015375:Receptors, Interleukin-2 / Q000032:analysis; D020395:Receptors, Interleukin-7 / Q000032:analysis; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014184:Transplantation, Homologous
D018960:Hyaluronan Receptors; D015851:Interleukin-7; D015375:Receptors, Interleukin-2; D020395:Receptors, Interleukin-7