CD8+HLA-DR+ T cells are increased in patients with severe aplastic anemia

Abstract

The aim of the present study was to investigate the number and function of CD8+HLA-DR+ cells, which are considered to be activated cytotoxic T lymphocytes (CTLs), in peripheral blood to further examine the pathogenesis of severe aplastic anemia (SAA). Thirty-eight patients with SAA were included in the present study. Patients were screened for paroxysmal nocturnal hemoglobinuria by flow cytometry using anti-CD55 and anti-CD59 antibodies. The number of CD8+HLA-DR+ T cells was measured by three-color flow cytometry using anti-CD8-peridinin chlorophyll, anti-CD3-fluorescein isothiocyanate (FITC) and anti-HLA-DR-FITC antibodies. The expression of perforin, granzyme B, tumor necrosis factor-β (TNF-β) and FasL in CD8+HLA-DR+ T cells was detected by flow cytometry with the appropriate monoclonal antibodies. Total RNA was prepared from purified CD8+HLA-DR+ cells of healthy controls and SAA patients, and then polymerase chain reaction (PCR) was performed. Apoptosis of CD8+HLA-DR+ cells was detected by flow cytometry following staining with Annexin V. The proportion of CD8+HLA-DR+ T cells was analyzed by flow cytometry in peripheral blood and was identified to be significantly higher in untreated SAA than in remission patients and in the controls. The expression of perforin, granzyme B, TNF-β and FasL in CD8+HLA-DR+ T cells was analyzed by flow cytometry and PCR, which revealed increased expression in the untreated SAA group compared with that in the control group. Furthermore, the apoptosis of CD3- bone marrow cells from normal individuals was enhanced following co-culture with CD8+HLA-DR+ T cells from untreated SAA patients. In conclusion, the present study demonstrated that CD8+HLA-DR+ T cells may contribute to bone marrow failure in SAA.

Increased Type 1 Immune Response in the Bone Marrow Immune Microenvironment of Patients with Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation

“…CD45RA þ CCR7 À , CD45RA þ CCR7 þ , CD45RA À CCR7 À , and CD45RA À CCR7 þ cells were identified as effector T cells, naïve T cells, effector memory T cells, and central memory T cells, respectively [31]. HLA-DR was identified as an active marker on T cells [32]. Data were analyzed using BD Diva software (BD Biosciences).…”

Identification of novel microRNA signatures linked to acquired aplastic anemia

“…These results are consistent with previous reports describing increased GZMB and IFN-γ expression in CD8 + T cells of AA patients. 2,27 We speculated that transfusion might affect the miRNA signatures in T cells as a result of allogenic antigen exposure in AA patients. 28 We, therefore, also examined miRNA profiles of T cells from age-matched healthy donors and patients with transfusion-dependent SCD and low-risk MDS for comparison with AA.…”

Epstein Barr Virus Infection Affects Function of Cytotoxic T Lymphocytes in Patients with Severe Aplastic Anemia

“…Proliferation and over activation of cytotoxic T lymphocytes (CTLs; CD8+ T cells) are the direct causes of bone marrow failure in patients with SAA [2]. Our group conducted a series of studies in which we found abnormal expression of various immunomodulatory molecules on the surface of CTLs and an increased number of activated effective T cells (CD8+ human leukocyte antigen D related + T cells), with obviously higher levels of intracellular molecules, including perforin, granzyme B, tumor necrosis factor (TNF) β , and FasL, which confirmed that CTLs may be key cells in the pathogenesis of SAA [3–5]. A variety of viruses are known to lead to hyperfunction of CTLs via disruption of the immune balance and ultimately contribute to the occurrence of SAA.…”