[The role of intracellular signal pathway of mTOR/S6 in CD3+ T lymphocytes of refractory/relapsed aplastic anemia patients].
OBJECTIVE
To 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.


METHODS
BM 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).


CONCLUSIONS
(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.
Zhang
Xiang
X
The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou 215006, China.
He
Guang-Sheng
GS
Wu
De-Pei
DP
Sun
Ai-Ning
AN
Miao
Miao
M
Wang
Xiu-Li
XL
Jin
Zheng-Ming
ZM
Qiu
Hui-Ying
HY
Chang
Wei-Rong
WR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000276:immunology / Q000378:metabolism*; D015703:Antigens, CD / Q000494:pharmacology; D060908:CTLA-4 Antigen; D002648:Child; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D038601:Ribosomal Protein S6 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D055815:Young Adult
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D038601:Ribosomal Protein S6; D007371:Interferon-gamma; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus