Regulatory T cell (Treg) subsets return in patients with refractory lupus following stem cell transplantation, and TGF-beta-producing CD8+ Treg cells are associated with immunological remission of lupus.
J Immunol
; 183(10): 6346-58, 2009 Nov 15.
Article
en En
| MEDLINE
| ID: mdl-19841178
ABSTRACT
Compared with conventional drug therapy, autologous hemopoietic stem cell transplantation (HSCT) can induce very-long-term remission in refractory lupus patients. Herein, we show that in posttransplant patients, both CD4(+)CD25(high)FoxP3(+) and an unusual CD8(+)FoxP3(+) Treg subset return to levels seen in normal subjects; accompanied by almost complete inhibition of pathogenic T cell response to critical peptide autoepitopes from histones in nucleosomes, the major lupus autoantigen from apoptotic cells. In addition to a stably sustained elevation of FoxP3, posttransplant CD8 T cells also maintained markedly higher expression levels of latency-associated peptide (LAP), CD103, PD-1, PD-L1, and CTLA-4, as compared with pretransplant CD8 T cells that were identically treated by a one-time activation and rest in short-term culture. The posttransplant CD8 regulatory T cells (Treg) have autoantigen-specific and nonspecific suppressive activity, which is contact independent and predominantly TGF-beta dependent. By contrast, the pretransplant CD8 T cells have helper activity, which is cell contact dependent. Although CD4(+)CD25(high) Treg cells return during clinical remission of conventional drug-treated lupus, the posttransplant patient's CD8 Treg cells are considerably more potent, and they are absent in drug-treated patients in whom CD4 T cell autoreactivity to nucleosomal epitopes persists even during clinical remission. Therefore, unlike conventional drug therapy, hemopoietic stem cell transplantation generates a newly differentiated population of LAP(high)CD103(high) CD8(TGF-beta) Treg cells, which repairs the Treg deficiency in human lupus to maintain patients in true immunological remission.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Subgrupos de Linfocitos T
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Linfocitos T Reguladores
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Trasplante de Células Madre Hematopoyéticas
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Linfocitos T CD8-positivos
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Lupus Eritematoso Sistémico
Tipo de estudio:
Risk_factors_studies
Límite:
Adolescent
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Adult
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Immunol
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos