The role of intracellular signal pathway of mTOR/S6 in CD3+ T lymphocytes of refractory/relapsed aplastic anemia patients.
- Author:
Xiang ZHANG
1
;
Guang-Sheng HE
;
De-Pei WU
;
Ai-Ning SUN
;
Miao MIAO
;
Xiu-Li WANG
;
Zheng-Ming JIN
;
Hui-Ying QIU
;
Wei-Rong CHANG
Author Information
- Publication Type:Journal Article
- MeSH: Adolescent; Adult; Aged; Anemia, Aplastic; immunology; metabolism; Antigens, CD; pharmacology; CTLA-4 Antigen; Child; Female; Humans; Interferon-gamma; metabolism; Male; Middle Aged; Ribosomal Protein S6; metabolism; Signal Transduction; drug effects; Sirolimus; pharmacology; T-Lymphocytes; immunology; metabolism; TOR Serine-Threonine Kinases; metabolism; Young Adult
- From: Chinese Journal of Hematology 2009;30(10):654-657
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo explore the activation status of signal pathway of mTOR/S6 in bone marrow (BM) T lymphocytes of refractory/relapsed aplastic anemia patients (AA), and the effects of rapamycin (RAPA) and CTLA-4 immunoglobulin (CTLA-4Ig) on this pathway.
METHODSBM was collected from 13 refractory/relapsed AA patients, 8 newly diagnosed severe AA (SAA) patients and 10 iron deficiency anemia (IDA) (as controls) patients, and cocultured with RAPA and CTLA-4 Ig. The expression of p-mTOR, p-S6 and Interferon gamma (IFN-gamma) in CD3(+)T cells was measured by flow cytometry (FCM).
RESULTS(1) The expression of p-mTOR, p-S6 and IFN-gamma in CD3(+)T cells in refractory/relapsed AA group were significantly higher than those in controls (P < 0.01). (2) The expression of p-mTOR and p-S6 in T cells in newly diagnosed SAA group, was similar to those in controls (P > 0.05), but significantly lower than those in refractory/relapsed AA group (P < 0.01). The expression level of IFN-gamma in T cells were significantly higher than that in controls (P < 0.01). (3) On exposure to RAPA, the levels of p-mTOR, p-S6 and IFN-gamma in T cells in refractory/relapsed AA patients were significantly lower than those before the exposure (all P < 0.05). And so were when exposed to CTLA-4 Ig (all P < 0.01).
CONCLUSION(1) The mTOR/S6 signal pathway is activated in refractory/relapsed AA. (2) The expression of p-mTOR, p-S6 and IFN-gamma in refractory/relapsed AA can be suppressed by RAPA or CTLA-4Ig. (3) The signal pathway of CD28/mTOR/S6/IFN-gamma might take part in immune pathogenesis of refractory/relapsed AA.
