Functional characterization of CD4+ T cells in aplastic anemia

he role of CD4(+) T-cells in the pathogenesis of AA is not well characterized. The focus of this study is to investigate the role of CD4(+) T-cells in AA with particular emphasis on CD4(+) regulatory and effector T-cell subsets and correlation with disease severity. 63 patients(48 at diagnosis) with acquired AA were studied. Numbers of Th1 and Th2-cells were significantly higher in AA compared with age matched healthy donors (HDs) (p=0.03) (p=0.006). Tregs were significantly lower in severe AA (SAA) and very severe AA (VSAA) compared to HDs (p<0.001) and non-severe AA (NSAA) patients (p=0.01). Th17-cells were increased in SAA and VSAA (p=0.02) but normal in NSAA. The percentage of both activated and resting Tregs was reduced in AA (p=0.004) (p=0.01), whereas cytokine secreting non-Tregs were increased (p=0.003). Tregs from AA patients were unable to suppress cytokine secretion by normal Te cells. In contrast, AA Te-cells were suppressible by Tregs from HDs. The frequency of major Th1 clones in AA, investigated by high throughput sequencing, were higher compared to HDs (p=0.03). Our results confirm that Th1 and Th2-cells are expanded and Tregs are functionally abnormal in AA. The clonally restricted expansion of Th1-cells is most likely to be antigen-driven, and by inducing an inflammatory environment, exacerbate the functional impairment of Tregs, that are reduced in number.