Title | Luteinizing hormone-releasing hormone enhances T cell recovery following allogeneic bone marrow transplantation. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Goldberg GL, King CG, Nejat RA, Suh DY, Smith OM, Bretz JC, Samstein RM, Dudakov JA, Chidgey AP, Chen-Kiang S, Boyd RL, van den Brink MRM |
Journal | J Immunol |
Volume | 182 |
Issue | 9 |
Pagination | 5846-54 |
Date Published | 2009 May 01 |
ISSN | 1550-6606 |
Keywords | Animals, Bone Marrow Cells, Bone Marrow Transplantation, Cell Differentiation, Female, Gonadotropin-Releasing Hormone, Graft vs Host Disease, Graft vs Tumor Effect, Hematopoietic Stem Cells, Humans, Isoantigens, Leuprolide, Lymphopenia, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Spleen, T-Lymphocytes, Thymus Gland |
Abstract | 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. |
DOI | 10.4049/jimmunol.0801458 |
Alternate Journal | J Immunol |
PubMed ID | 19380833 |
PubMed Central ID | PMC2760441 |
Grant List | R01 HL069929 / HL / NHLBI NIH HHS / United States R01 AI080455-01 / AI / NIAID NIH HHS / United States R01 HL069929-07 / HL / NHLBI NIH HHS / United States R01 HL069929-03 / HL / NHLBI NIH HHS / United States R01 CA107096-05 / CA / NCI NIH HHS / United States R01 CA107096-01A1 / CA / NCI NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States R01 CA107096-03 / CA / NCI NIH HHS / United States R01 CA107096-04 / CA / NCI NIH HHS / United States R01 HL069929-01 / HL / NHLBI NIH HHS / United States T32 GM007739 / GM / NIGMS NIH HHS / United States R01 HL069929-06 / HL / NHLBI NIH HHS / United States R01 HL069929-05A1 / HL / NHLBI NIH HHS / United States R01 HL069929-02 / HL / NHLBI NIH HHS / United States R01 CA107096-02 / CA / NCI NIH HHS / United States R01 CA107096 / CA / NCI NIH HHS / United States R01 AI080455-02 / AI / NIAID NIH HHS / United States P01 CA033049-250016 / CA / NCI NIH HHS / United States P01-CA33049 / CA / NCI NIH HHS / United States R01 AI080455 / AI / NIAID NIH HHS / United States P01 CA033049 / CA / NCI NIH HHS / United States R01-HL069929 / HL / NHLBI NIH HHS / United States R01 HL069929-08 / HL / NHLBI NIH HHS / United States R01 HL069929-04 / HL / NHLBI NIH HHS / United States R01-CA107096 / CA / NCI NIH HHS / United States R01-AI080455 / AI / NIAID NIH HHS / United States P01 CA033049-260016 / CA / NCI NIH HHS / United States |
Related Faculty:
Selina Chen-Kiang, Ph.D.