Postgrafting administration of granulocyte colony-stimulating factor impairs functional immune recovery in recipients of human leukocyte antigen haplotype–mismatched hematopoietic transplants
| Autor: | Franco Aversa, Katia Perruccio, Massimo F. Martelli, Isabella Volpi, Antonella Tosti, Antonio Tabilio, Marusca Capanni, Luigina Romani, Loredana Ruggeri, Sabrina Posati, Andrea Velardi |
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| Rok vydání: | 2001 |
| Předmět: |
Adult
Male Adolescent Immunology Antigen presentation Graft vs Host Disease Human leukocyte antigen Biology medicine.disease_cause Biochemistry Th2 Cells Immune system Immunopathology Granulocyte Colony-Stimulating Factor medicine Humans Child Candida Salvage Therapy Leukemia Graft Survival Hematopoietic Stem Cell Transplantation Immunologic Deficiency Syndromes Receptors Interleukin-12 Dendritic Cells Receptors Interleukin Cell Biology Hematology Middle Aged Immune dysregulation Interleukin-12 Hematopoietic Stem Cell Mobilization CD4 Lymphocyte Count Interleukin-10 Granulocyte colony-stimulating factor Transplantation Protein Subunits Aspergillus Treatment Outcome Haplotypes Child Preschool Acute Disease Interleukin 12 Female Disease Susceptibility Interleukin-4 Immunologic Memory |
| Zdroj: | Blood. 97:2514-2521 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v97.8.2514 |
| Popis: | In human leukocyte antigen haplotype–mismatched transplantation, extensive T-cell depletion prevents graft-versus-host disease (GVHD) but delays immune recovery. Granulocyte colony-stimulating factor (G-CSF) is given to donors to mobilize stem cells and to recipients to ensure engraftment. Studies have shown that G-CSF promotes T-helper (Th)-2 immune deviation which, unlike Th1 responses, does not protect against intracellular pathogens and fungi. The effect of administration of G-CSF to recipients of mismatched hematopoietic transplants with respect to transplantation outcome and functional immune recovery was investigated. In 43 patients with acute leukemia who received G-CSF after transplantation, the engraftment rate was 95%. However, the patients had a long-lasting type 2 immune reactivity, ie, Th2-inducing dendritic cells not producing interleukin 12 (IL-12) and high frequencies of IL-4– and IL-10–producing CD4+ cells not expressing the IL-12 receptor β2 chain. Similar immune reactivity patterns were observed on exposure of donor cells to G-CSF. Elimination of postgrafting administration of G-CSF in a subsequent series of 36 patients with acute leukemia, while not adversely affecting engraftment rate (93%), resulted in the anticipated appearance of IL-12–producing dendritic cells (1-3 months after transplantation versus > 12 months in transplant recipients given G-CSF), of CD4+ cells of a mixed Th0/Th1 phenotype, and of antifungal T-cell reactivity in vitro. Moreover, CD4+ cell counts increased in significantly less time. Finally, elimination of G-CSF–mediated immune suppression did not significantly increase the incidence of GVHD (< 15%). Thus, this study found that administration of G-CSF to recipients of T-cell–depleted hematopoietic transplants was associated with abnormal antigen-presenting cell functions and T-cell reactivity. Elimination of postgrafting administration of G-CSF prevented immune dysregulation and accelerated functional immune recovery. |
| Databáze: | OpenAIRE |
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