[Significance of CD4+ CD25+ CD127(low) regulatory T cells and notch1 pathway in the pathogenesis of aplastic anemia].
OBJECTIVE
To quantify the CD4+ CD25+ CD127(low) regulatory T cell (Treg), the expression levels of forkhead/winged helix transcription factor FOXP3 and Notch1 mRNA in aplastic anemia (AA) patients before and after treatment, and explore the significance of Treg in pathogenesis of AA.


METHODS
CD4+ CD25+ and CD4+ CD25+ CD127(low) T cells in peripheral blood were examined with FACS in 29 AA patients at active phase, 14 at recovery phase, 11 at unrecovery phase, and 15 normal controls. The levels of FOXP3 mRNA and Notch1 mRNA expression were detected with RT-PCR, and the correlations between Treg, FOXP3 mRNA and Notchl mRNA were analyzed.


RESULTS
The percentages of peripheral activated CD4+ CD25+ T cells in AA patients at active phase (4.3 +/- 0.7)% and unrecovery phase (4.2 +/- 0.6)% were significantly higher than those in normal controls (2.4 +/- 0.8)% (P < 0.05). The proportion of these cells in AA patients at recovery phase was reduced to (2.6 +/- 0.7)% (P < 0.05), being no difference from that in control group. The number of CD4+ CD25+ CD127(low) T cells in AA patients at active phase (2.4 +/- 1.2)% and unrecovery phase (2.5 +/- 1.1)% was decreased significantly compared with those in normal controls (7.1 +/- 2.7)% (P < 0.01) and in AA patients at recovery phase (5.3 +/- 1.0)% (P < 0.01), there was no difference between the latter two groups. In active phase AA patients, the levels of FOXP3 mRNA and Notchl mRNA (0.260 +/- 0.011 and 0.018 +/- 0.005, respectively) were lower than that in control group (1.307 +/- 0.011 and 0.308 +/- 0.028, respectively) (P < 0.01 and P < 0.01). After treatment, the levels significantly increased to 1.287 +/- 0.012 and 0.281 +/- 0.013 (P < 0.01 and P < 0.01), but there was no difference with that of normal controls (P > 0.05). CD4+ CD25+ CD2(low) T cells and FOXP3 were positively related with Notchl (P < 0.01) in AA patients.


CONCLUSIONS
The decreased number and suppressive activity of CD4 CD25+ CD127(low) Treg cells in the peripheral blood of AA patients cause over-activation of autoreactive T cells and suppression of haematopoiesis. One of the mechanisms maybe the reduced expression of Notch1 in the target cells.
Department of Hematology, Qilu Hospital of Shandong University, Jinan 250012, China.
Xiao-Xiao
XX
Yin
Chuan-Fang
CF
Liu
Li-Zhen
LZ
Li
Wei-Zhi
WZ
Chen
D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000276:immunology* / Q000378:metabolism; D015704:CD4 Antigens; D016022:Case-Control Studies; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D012333:RNA, Messenger; D051881:Receptor, Notch1