Luteinizing hormone-releasing hormone enhances T cell recovery following allogeneic bone marrow transplantation.
Posttransplant immunodeficiency, specifically a lack of T cell reconstitution, is a major complication of allogeneic bone marrow transplantation. This immunosuppression results in an increase in morbidity and mortality from infections and very likely contributes to relapse. In this study, we demonstrate that sex steroid ablation using leuprolide acetate, a luteinizing hormone-releasing hormone agonist (LHRHa), increases the number of lymphoid and myeloid progenitor cells in the bone marrow and developing thymocytes in the thymus. Although few differences are observed in the peripheral myeloid compartments, the enhanced thymic reconstitution following LHRHa treatment and allogeneic bone marrow transplantation leads to enhanced peripheral T cell recovery, predominantly in the naive T cell compartment. This results in an increase in T cell function in vivo and in vitro. Graft-versus-host-disease is not exacerbated by LHRHa treatment and graft-versus-tumor activity is maintained. Because LHRHa allows for reversible (and temporary) sex steroid ablation, has a strong safety profile, and has been clinically approved for diseases such as prostate and breast cancer, this drug treatment represents a novel therapeutic approach to reversal of thymic atrophy and enhancement of immunity following immunosuppression.
Goldberg
Gabrielle L
GL
Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
King
Christopher G
CG
Nejat
Rebecca A
RA
Suh
David Y
DY
Smith
Odette M
OM
Bretz
Jamison C
JC
Samstein
Robert M
RM
Dudakov
Jarrod A
JA
Chidgey
Ann P
AP
Chen-Kiang
Selina
S
Boyd
Richard L
RL
van den Brink
Marcel R M
MR
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage* / Q000819:agonists; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology / Q000628:therapy; D020350:Graft vs Tumor Effect / Q000187:drug effects / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D006801:Humans; D007519:Isoantigens / Q000008:administration & dosage / Q000235:genetics; D016729:Leuprolide / Q000008:administration & dosage; D008231:Lymphopenia / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000473:pathology / Q000637:transplantation*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D007519:Isoantigens; D007987:Gonadotropin-Releasing Hormone; D016729:Leuprolide