Luteinizing hormone-releasing hormone enhances T cell recovery following allogeneic bone marrow transplantation Journal Article
| Authors: | Goldberg, G. L.; King, C. G.; Nejat, R. A.; Suh, D. Y.; Smith, O. M.; Bretz, J. C.; Samstein, R. M.; Dudakov, J. A.; Chidgey, A. P.; Chen-Kiang, S.; Boyd, R. L.; van den Brink, M. R. M. |
| Article Title: | Luteinizing hormone-releasing hormone enhances T cell recovery following allogeneic bone marrow transplantation |
| 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. Copyright © 2009 by The American Association of Immunologists, Inc. |
| Keywords: | controlled study; genetics; drug potentiation; drug safety; nonhuman; t lymphocyte; t-lymphocytes; animal cell; mouse; animal; cytology; animals; mice; bone marrow cells; spleen; animal experiment; animal model; allogenic bone marrow transplantation; cell differentiation; drug effect; pathology; transplantation; mice, inbred balb c; mice, inbred c57bl; gonadorelin; c57bl mouse; lymphocytopenia; leuprorelin; immunology; bagg albino mouse; thymus; thymus gland; graft versus host reaction; hematopoietic stem cells; bone marrow cell; hematopoietic stem cell; immune deficiency; immunosuppressive treatment; bone marrow transplantation; graft vs host disease; lymphoid progenitor cell; thymus atrophy; gonadotropin-releasing hormone; alloantigen; graft versus leukemia effect; myeloid progenitor cell; thymocyte; graft vs tumor effect; isoantigens; leuprolide; lymphopenia |
| Journal Title: | Journal of Immunology |
| Volume: | 182 |
| Issue: | 9 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2009-05-01 |
| Start Page: | 5846 |
| End Page: | 5854 |
| Language: | English |
| DOI: | 10.4049/jimmunol.0801458 |
| PUBMED: | 19380833 |
| PROVIDER: | scopus |
| PMCID: | PMC2760441 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 8" - "Export Date: 30 November 2010" - "CODEN: JOIMA" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work