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Replacement therapy with plasma-derived factor VIII concentrates induces skew in T-cell receptor usage and clonal expansion of CD8+ T-cell in HIV-seronegative hemophilia patients
- Source :
- Thrombosis and Haemostasis. 90:279-292
- Publication Year :
- 2003
- Publisher :
- Georg Thieme Verlag KG, 2003.
-
Abstract
- SummaryReplacement therapy with factor VIII (FVIII) products causes immune abnormalities in human immunodeficiency virus (HIV)-seronegative hemophilia patients. However, the question remains why an absolute increase in the number of CD8+ T-cells and diminished proliferation responses of lymphocytes to antigen stimulation in vitro occurs in HIV-seronegative hemophilia patients.To examine whether the FVIII products induce skewing of T-cell receptor (TCR) repertoires, TCR variable region α-chain and β–chain repertoires were analyzed for peripheral blood mononuclear cells (PBMCs) from 15 hemophilia patients treated with heated and/or non-heated plasma-derived FVIII concentrates and 10 age-matched healthy adults. Also, T-cell clonality was compared between these groups using complementarity-determining region 3 (CDR3) size spectratyping. The skewing of TCR repertoires was significantly greater for hemophilia patients than healthy controls. The extent of T-cell clonality was greater for hemophilia patients than the controls, indicating that clonal T-cells frequently expanded in hemophilia patients. The skew in TCR usage and clonal expansion were primarily observed in patients treated with non-heated plasma-derived products.The spectratyping and sequencing of CDR3 regions revealed that the clonal expansion of T-cells was observed for CD8+ T-cells, but not CD4+ T-cells.These results suggest that extensive expansion of CD8+ T-cells is induced by some viruses other than HIV present in FVIII preparations, and the resulting accumulation of CD8+ T-cells is responsible for changes in peripheral T-cell population in HIV-seronegative hemophilia patients.
- Subjects :
- Adult
congenital, hereditary, and neonatal diseases and abnormalities
Adolescent
Receptors, Antigen, T-Cell, alpha-beta
T cell
Population
CD8-Positive T-Lymphocytes
Hemophilia A
Peripheral blood mononuclear cell
Monocytes
Antigen
HIV Seronegativity
hemic and lymphatic diseases
medicine
Coagulopathy
Humans
Cytotoxic T cell
Child
education
education.field_of_study
Factor VIII
business.industry
T-cell receptor
Hematology
medicine.disease
Complementarity Determining Regions
Clone Cells
medicine.anatomical_structure
Case-Control Studies
Immunology
business
Cell Division
CD8
Subjects
Details
- ISSN :
- 2567689X and 03406245
- Volume :
- 90
- Database :
- OpenAIRE
- Journal :
- Thrombosis and Haemostasis
- Accession number :
- edsair.doi.dedup.....38d7b2199470feec699ca9f3d70df4f0
- Full Text :
- https://doi.org/10.1160/th02-12-0302