Increased CD4+ and CD8+ effector memory T cells in patients with aplastic anemia.

In the present study, we initially reported that the percentages of CD4 + and CD8 + effector memory T cells (TEM cells) were increased in PB and BM of AA. The elevated TEM cells with the potent effector capacity may relate to the abnormal immune status in the pathogenesis of AA. T-cell mediated suppression of hematopoiesis is considered the pivotal mechanism responsible for bone marrow failure in aplastic anemia (AA). 1 In patients with AA, oligoclonal T cells in marrow were detected to show mature memory/effector phenotypes, 2 implicating memory T cells might participate in the pathophysiological process of AA. Based on the ability to express chemokine receptor CCR7 and the phosphatase CD45RA, CD4 + and CD8 + , T cells can be divided into naïve T cells (CD45RA + CCR7 +), central memory T cells (TCM cells, CD45RA – CCR7 +), and effector memory T cells (TEM cells, CD45RA – CCR7 –). For CD8 + T cells, TEM cells also contain terminally differentiated CD45RA + CCR7 – TEM cells (terminal TEM cells). 3,4 Perturbation in the homeostasis of memory T cells has been reported in several T-cell mediated autoimmune diseases. 5-7 In the present study, we initially investigated the distribution and function of naïve T cells, TCM cells, and TEM cells in patients with AA. The study was approved by the Ethics Committee of Qilu Hospital, Shandong University, and informed consent was obtained from each participant. Forty-five newly-diagnosed untreated patients with AA (23 males and 22 females, mean age 36 years, range 18-69) were enrolled in this study. Criteria for the diagnosis and severity classification of AA were as previously reported. Out of 45 patients, 27 patients were diagnosed with severe AA (SAA) and 18 patients with moderate AA (MAA). No patient with AA had received any treatment or transfusion before enrollment. Thirty gender-and age-matched healthy volunteers served as controls (16 males, 14 females, mean age 41 years, range 21-67). Freshly isolated peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMMNCs) were stained with FITC-conjugated anti-to measure percentages of naïve T cells, TCM cells and TEM cells in CD4 + and CD8 + T cells in both PBMCs and BMMNCs. For the important pathogenic role of T cell-produced IFN-γ in AA, intracellular cytokine IFN-γ production by different T-cell subsets was detected to assess their function. PBMCs and BMMNCs were simulated with 25 ng/mL PMA and 1 umol/L …