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Postgrafting administration of granulocyte colony-stimulating factor impairs functional immune recovery in recipients of human leukocyte antigen haplotype–mismatched hematopoietic transplants
- Source :
- Blood. 97:2514-2521
- Publication Year :
- 2001
- Publisher :
- American Society of Hematology, 2001.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 97
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....25591fce06a11452bf6ade0d70ecceca