Back to Search
Start Over
Double-negative regulatory T cells induce allotolerance when expanded after allogeneic haematopoietic stem cell transplantation
- Source :
- British Journal of Haematology. 141:170-178
- Publication Year :
- 2008
- Publisher :
- Wiley, 2008.
-
Abstract
- Double-negative (DN) regulatory T cells (Tregs) are specialized T lymphocytes involved in the down-modulation of immune responses, resulting in allotolerance after allogeneic haematopoietic stem cell transplantation (HSCT). Most of the properties of DN Tregs were identified in murine models, including the unique ability to suppress alloreactive syngeneic effector T cells in an antigen-specific manner via Fas/Fas-ligand interactions. We investigated the behaviour of DN Tregs following human allogeneic HSCT with regard to occurrence of graft-versus-host disease (GvHD) and restoration of T-cell receptor repertoire in a cohort of 40 patients. The frequency of DN Tregs and CD4/CD8 TCR repertoire was measured serially and at the time of diagnosis of GvHD by flow cytometry. Analysis demonstrated a positive correlation between degree of alloreactivity, as measured by grade of GvHD, and the number of variable beta chain (Vbeta) family expansions in both T-cell populations. We also found that a deficiency of DN Tregs was associated with an increased number of Vbeta family expansions, and most importantly, with the occurrence of GvHD. All individuals who demonstrated more than 1% DN Tregs did not develop GvHD, providing evidence that DN Tregs participate in peripheral tolerance to prevent GvHD when expanded after allogeneic HSCT.
- Subjects :
- Adult
Male
medicine.medical_treatment
Graft vs Host Disease
chemical and pharmacologic phenomena
Hematopoietic stem cell transplantation
Biology
Severity of Illness Index
T-Lymphocytes, Regulatory
Immune tolerance
T-Lymphocyte Subsets
immune system diseases
Immune Tolerance
medicine
Humans
Aged
Hematopoietic Stem Cell Transplantation
Peripheral tolerance
Forkhead Transcription Factors
hemic and immune systems
Hematology
Middle Aged
medicine.disease
Transplantation
Haematopoiesis
surgical procedures, operative
Graft-versus-host disease
Immunology
Female
Stem cell
CD8
Follow-Up Studies
Subjects
Details
- ISSN :
- 13652141 and 00071048
- Volume :
- 141
- Database :
- OpenAIRE
- Journal :
- British Journal of Haematology
- Accession number :
- edsair.doi.dedup.....317a849fb293ecbbb5a7ad060c1e8ffd