| Autor: |
Clark, Fiona J., Gregg, Richard, Piper, Karen, Dunnion, Debbie, Freeman, Lisa, Griffiths, Mike, Begum, Gulnaz, Mahendra, Premini, Craddock, Charles, Moss, Paul, Chakraverty, Ronjon |
| Zdroj: |
Blood; March 2004, Vol. 103 Issue: 6 p2410-2416, 7p |
| Abstrakt: |
Chronic graft-versus-host disease (cGVHD) is characterized by a state of profound immunodeficiency in association with alloreactive and autoimmune phenomena. These observations indicate an impairment of immunologic tolerance that could involve both central and peripheral mechanisms. Defective thymic function may contribute to dysregulation of central tolerance, but few studies have addressed peripheral tolerance. Recently a population of CD4+CD25+T cells (Tregcells) has been characterized, which controls immunologic reactivity in vivo and which on transfer can prevent experimental acute GVHD. We investigated the number and function of peripheral blood CD4+CD25highT cells in patients more than 100 days after allogeneic hematopoietic stem cell transplantation. Patients with cGVHD had markedly elevated numbers of CD4+CD25highT cells as compared to patients without GVHD. CD4+CD25highT cells derived from patients in both groups were of donor origin, lacked markers of recent activation, and expressed intracellular CD152. In contrast to controls, CD4+CD25highT cells derived from patients with cGVHD were characterized by lower surface CD62L expression. In vitro, CD4+CD25highT cells were hyporesponsive to polyclonal stimulation and suppressed the proliferation and cytokine synthesis of CD4+CD25-cells, an effect that was independent of interleukin 10. These results indicate that chronic graft-versus-host injury does not occur as a result of Tregcell deficiency. |
| Databáze: |
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