Study on the Dendritic Cell Subsets and Their Relationship with the Expressions of T-Bet and GATA-3 in Peripheral Lymphocytes of Severe Aplastic Anemia Patients

Objective To investigate the effects of the dendritic cell (DC) subsets and the transcriptive factors, T-bet and GATA-3, on immune imbalance in the pathogenesis of acquired severe aplastic anemia (SAA).

Methods The mDCs(HLA-DR⁺Lin⁻CD11c⁺) and pDCs(HLA-DR⁺Lin⁻CD123⁺) in peripheral blood mononuclear cells (PBMNC) were measured with flow cytometry (FCM), the expressions of T-bet mRNA and GATA-3 mRNA in PBMNC with semiquantitive RT-PCR and the plasma levels of IFNγ and IL-4 with ELISA in 29 SAA patients (21 untreated and 8 recovered) and 16 healthy controls.

Results The percentages of mDCs in PBMNC were (0.44±0.24) % and (0.73±0.30) % in untreated and recovered SAA patients respectively, either of which was higher than that of controls (0.29±0.10%) (P<0.05). The percentage of pDCs in the untreated cases was lower than that of the recovered or controls [(0.18±0.14) % vs. (0.28±0.20) % and (0.29±0.13) %] (P<0.05). mDCs/pDCs ratios were 3.45±2.71 and 2.90±0.95 in untreated and recovered groups respectively, either of which was higher than that of controls (1.15±0.56) (P<0.05). No statistical difference of mDCs/pDCs was found between untreated and recovered patients (P<0.05). The relative mRNA expressions of transcriptive factor T-bet were 0.37±0.07, 0.20±0.07 and 0.17±0.05 in 3 groups, respectively. The expression of T-bet of untreated patients was higher than that of recovered patients or healthy controls (P<0.05). There was no statistical difference of GATA-3 expression among 3 groups(P>0.05). T-bet/GATA-3 ratio was 0.72±0.13 in untreated patients, which was higher than that of recovered patients (0.33±0.08) or controls (0.35±0.11). The plasma level of IFNγ in the untreated cases was (50.9±1.1)ng/L, which was higher than that of recovered [(49.7±0.9) ng/L] or controls[(49.7±0.7) ng/L]. There were significant positive correlation between T-bet and mDCs/pDCs (r=0.445, P<0.01), as well as T-bet and IFNγ (r=0.402, P<0.01).

Conclusion Both mDCs/pDCs and T-bet/GATA-3 ratios in SAA were higher and positively correlated which might contribute to the cascade activation of T lymphocytes. Immunosuppressive therapy for SAA should be kept on until both ratios become normal.