IL-7-mediated protection against minor-antigen-mismatched allograft rejection is associated with enhanced recovery of regulatory T cells.
OBJECTIVE
Interleukin-7 (IL-7) has been studied for its possible immunorestorative capacities following stem cell transplantation and has been shown to enhance post-transplant immune recovery predominantly by peripheral T-cell expansion. A major concern of IL-7 is its possible aggravating effect on graft-versus-host and host-versus-graft reactivity.


METHODS
To study the effect of IL-7 on host-versus-graft reactivity, we applied IL-7 in an experimental transplantation model using RAG-1-/- mice supplied with B6 CD45.1 congenic T cells as recipients of T-cell depleted allogeneic bone marrow grafts.


RESULTS
Rejection of minor antigen-mismatched bone marrow was significantly reduced in IL-7 treated recipients compared with PBS treated control mice. Rejection was observed in 2 out of 18 IL-7 treated mice compared with 9 out of 17 PBS treated mice (11% vs. 53%; p=0.012). IL-7 administration resulted in enhanced recovery of peripheral blood CD4+CD25+ regulatory T cells (Treg) with a concomitant increase in peripheral blood Foxp3 mRNA expression. IL-7Ra (CD127) was expressed by the vast majority of CD4+Foxp3+ T cells. The incidence of graft rejection following fully MHC mismatched bone marrow transplantation was not reduced nor enhanced by IL-7 administration.


CONCLUSIONS
Post-transplant IL-7 administration protects against minor antigen-mismatched bone marrow rejection, which may be due to enhanced Treg recovery.
Broers
Annoek E C
AE
Department of Hematology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
Bruinsma
Marieke
M
Posthumus-van Sluijs
Sandra J
SJ
Wils
Evert-Jan
EJ
Spits
Hergen
H
Löwenberg
Bob
B
Braakman
Eric
E
Cornelissen
Jan J
JJ
D000818:Animals; D020296:Animals, Congenic; D016026:Bone Marrow Transplantation / Q000276:immunology*; D015704:CD4 Antigens / Q000032:analysis; D004353:Drug Evaluation, Preclinical; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006789:Host vs Graft Reaction / Q000187:drug effects*; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D015851:Interleukin-7 / Q000494:pharmacology / Q000627:therapeutic use*; D053699:Interleukin-7 Receptor alpha Subunit / Q000096:biosynthesis / Q000235:genetics; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013047:Specific Pathogen-Free Organisms; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D014184:Transplantation, Homologous
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; D015778:Minor Histocompatibility Antigens; D011994:Recombinant Proteins