Aplastic anemia (AA) is an autoimmune disease characterized by destruction of hematopoietic tissue resulting in hyperfunction of effector T-lymphocytes. Recent studies indicate that Th17 and Treg cells are functionally antagonistic each other, and the increase of Th17 cells and decrease of Treg cells are closely related with AA. In vivo experiments showed that both anti-IL-17 treatment and Treg cell infusion can protect against immune-mediated bone marrow failure in mouse with AA. This review summarizes the recent progress of study on imbalance of Th17/Treg cells in AA, so as to explore the pathogenesis of AA and provide approach to clinical treatment. The main problems that are discussed in this review include biological characteristics of Th17/Treg cells, the regulation of Th17/Treg cell balance and related cytokines, the relationship between Th17/Treg cells and AA.
Anemia, Aplastic ; immunology ; pathology ; Humans ; T-Lymphocytes, Regulatory ; immunology ; Th17 Cells ; immunology

During the past few years, a novel family of CD4⁺T cell lineage was detected and named as Th17 cells because of its unique ability expressing IL-17, which also can produce IL-17A, IL-17F, IL-21, IL-22 and IL-26. Some cytokines, such as TGF-β, IL-6, L-23 may promote the differentiation of Th17 subset, whereas some cytokines, such as IL-21, IL-2, IFN-γ, may have inhibitory effects. Th17 cells serving as immune effectors play an important role in autoimmune diseases caused by chronic inflammation injury. More and more studies confirmed that Th17 cells have closely correlations with the development of aplastic anemia, and may be a new target in the diagnosis, therapy, prognosis and prophylaxis of aplastic anemia.
Anemia, Aplastic ; immunology ; Autoimmune Diseases ; Cell Differentiation ; Cytokines ; Humans ; Inflammation ; Th17 Cells ; cytology ; immunology

OBJECTIVES: To quantitate apoptosis and Fas antigen expression of T lymphocytes by activation in aplastic anemia (AA) and compare with that of normal controls and completely-recovered AA, and to investigate the apoptotic sensitivity to anti-fas antibody of activated T lymphocytes in AA. METHODS: We studied the expression of Fas antigen on fresh T lymphocytes of twenty patients with AA [13 newly diagnosed, 7 recorvered AA after immunosuppressive therapy (IST)], and investigated the activation-induced cell death (AICD) and Fas expression by activation [interleukin-2 (200 U/ml) and phytohemagglutinin (50 micrograms/ml)] in 5 newly-diagnosed AA, 5 normal controls and 5 AA in complete response (CR). Apoptotic sensitivity to anti-Fas antibody was assessed by the time-course kinetics of induction of cell death by anti-Fas antibody (500 ng/ml). RESULTS: There was no significant difference of Fas antigen expression on freshly-isolated T lymphocytes among newly-diagnosed severe AA, normal control s and patients with AA in CR after IST. In normal controls, T lymphocytes death was greatly increased at 3 days of activation, and Fas antigen expression on T lymphocytes was increased above baseline at day 1 of activation. In contrast, in newly-diagnosed AA, T lymphocytes showed delayed cell death, which correlated with a slowed increase of Fas antigen expression by activation. Also, anti-Fa s antibody sensitivity of activated T lymphocytes was decreased in newly-diagnosed AA. In completely recovered AA, these abnormal AICD and Fas antigen expressions by activation were recovered to normal range. CONCLUSIONS: Abnormal AICD plays a role in the immune pathophysiology of AA, and defective Fas system is involved in this process.
Anemia, Aplastic/pathology ; Anemia, Aplastic/immunology* ; Antigens, CD95/blood ; Apoptosis ; Case-Control Studies ; Human ; In Vitro ; Lymphocyte Transformation ; T-Lymphocytes/pathology* ; T-Lymphocytes/immunology* ; Time Factors

Aplastic anemia (AA) is a bone marrow failure disease caused by abnormal activation of T lymphocytes, resulting in the apoptosis of hematopoietic cells and bone marrow failure. Currently, hematopoietic stem cell transplantation (HSCT), immunosuppressive - therapy (IST), and supportive care (e.g. transfusion adjuvant therapy, hematopoietic growth factors, and prevention of infection) are the main treatments of AA. Granulocyte transfusion has recently been accepted as an useful adjuvant therapy of HSCT and intensive IST. This article reported a severe AA patient who failed to respond to IST, but achieved spontaneous remission three times after granulocyte transfusions from related donors. Such cases have rarely been reported. Existence of human leukocyte antigen (HLA) cross between the patient and his relatives may influence the T cell-mediated immunity, which might explain this patient's recovery.
Adult ; Anemia, Aplastic ; immunology ; physiopathology ; therapy ; Granulocytes ; transplantation ; Humans ; Leukocyte Transfusion ; Male ; Remission, Spontaneous

OBJECTIVETo study the clinical features of hepatitis-associated aplastic anemia (HAAA) in children.

METHODSThe clinical data of the children with newly diagnosed HAAA from January 2007 to December 2008 were respectively studied, including clinical manifestations, and blood routine, bone marrow examination, viral serology and immune function results as well as treatment and prognosis.

RESULTSA total of 8 children were confirmed as HAAA, accounting for 4.9% in children with aplastic anemia. There were 7 males and 1 female. The median age was 7.5 years (range 4.4 to 10.3 years) at diagnosis. They had negative serologic results and the causes of hepatitis could not be identified. The median interval from hepatitis occurrence to blood cell reduction was 6 weeks. Three cases were diagnosed as severe aplastic anemia and 5 cases as very severe aplastic anemia. Severe T cell immune disorders were found in all 8 cases. The percentage of Ts cells increased and the percentage of Th cells decreased significantly in the 8 children with HAAA. Four children survived after immune suppress treatment, three children died within one month after diagnosis and one child required own discharge without treatment.

CONCLUSIONSHAAA is more frequent in male school children. The children with HAAA have severe T cell immune disorders, with a higher early death rate. Immune suppress treatment is effective.

Anemia, Aplastic ; etiology ; immunology ; therapy ; Child ; Child, Preschool ; Female ; Hepatitis ; complications ; Humans ; Male ; Prognosis

Anemia, Aplastic ; drug therapy ; immunology ; Animals ; Antilymphocyte Serum ; immunology ; therapeutic use ; Calcineurin Inhibitors ; immunology ; therapeutic use ; Humans ; Immunoglobulins ; immunology ; therapeutic use ; Lymphocytes ; drug effects ; immunology ; Swine

The purpose of this study was to explore the clinical value of the platelet antibody screening and typing in platelets transfusion by using microcolumn gel immunoassay (MGIA). The platelets antigen-antibody reactions including the antibody screen and blood crossmatch were detected by MGIA. The results indicated that the detection of platelet antibody showed positive in 30 cases of aplastic anemia (AA), 11 cases of myelodysplastic syndrome (MDS), 24 out of 25 cases of leukemia and 1 out of cases of other diseases, while detection of platelet antibody showed negative in 20 normal volunteer donors. The number of platelet antibody crossmatch coincidence in 112 specimens of AA, 42 specimens of MDS and 95 specimens of leukemia were 45, 20 and 40, the coincidence rates were 40.18%, 47.62% and 42.11%. The mean corrected count increment (CCI) in 20 patients received platelet transfusion many times was 18.2 after crossmatch and 4.7 before crossmatch. It is concluded that the positive rate of platelet antibody screening is very high in patients with hematologic malignancies, the coincidence rate of platelet antibody crossmatch in 249 blood samples is between 40% and 48%, and the efficiency of using crossmatched platelets in clinic is enhanced significantly.
Anemia, Aplastic ; immunology ; Antigens, Human Platelet ; immunology ; Blood Grouping and Crossmatching ; Blood Platelets ; immunology ; Hematologic Neoplasms ; immunology ; Humans ; Immunoassay ; methods ; Isoantibodies ; blood ; immunology ; Platelet Transfusion ; methods

The study was aimed to investigate the changes of T-cell subgroups in the peripheral blood (PB) of patients with aplastic anemia (AA) and the relationships between these changes and the pathogenesis of AA and the immunosuppressive therapeutic effects in AA, in order to provide a basis for selecting rational therapy of AA patients. T-cell subtype and the ratio of CD4+/CD8+ cell in the PB of 88 AA patients which had been diagnosed clearly and given conventional therapy or conventional therapy combined with immunotherapy were analyzed by tri-colour fluorescence-labeled monoclonal antibody and using multiparameter flow cytometry. The patients with AA were divided into normal type of ratio, inverted type of ratio, hypernormal type of ratio according to the ratio of CD4+/CD8+ cell in normal group, and then the relations of these subtype with patients' conditions and therapeutic effects were investigated. The results showed that the percentage of normal type of ratio in all patients was 39.8%, the percentage of inverted type of ratio in all patients was 44.3%, The percentage of hypernormal type of ratio in all patients was 15.9%. In the conventional therapy alone, there was no significant difference on therapeutic effects among these three immunological subtypes. In combined immunotherapy, total therapeutic efficacy of AA patients with inverted type of ratio and AA patients with immunologic abnormality (inverted type + hypernormal type) was 84.2% and 82.6% respectively, which were more than that in conventional therapy (45.5% and 42.8%) (p < 0.05). Total therapeutic efficacy in these patients was better than that in AA patients with normal type. It is concluded that significant abnormal ratios of CD4+/CD8+ exist in the majority of AA patients, abnormal ratios of CD4+/CD8+ both may be showed as increase or decrease, immunologic abnormality may play a role in pathogenesis of the patients with AA. The detection of PB T-cell subtype in patients with aplastic anemia contributes to evaluation of patients' condition and choice of rational treatment prescription, and enhancement of diagnostic level and therapeutic efficacy significantly, which is an important indicator for therapeutic strategy also.
Adult ; Anemia, Aplastic ; immunology ; CD4-CD8 Ratio ; Female ; Humans ; Male ; Middle Aged ; T-Lymphocyte Subsets ; cytology ; immunology ; Young Adult

Aplastic anemia(AA) is mostly considered as an immune-mediated bone marrow failure syndrome, characterized by pancytopenia and bone marrow hypoplasia. The pathogenesis of AA is complicated, until now it is not fully understood. Further study on the pathological mechanism will be helpful for the diagnosis and treatment of AA. CD8(+) T cells and their secreted cytokines play important roles in the abnormal immunity during the process of AA. Thus, this review focuses on the role of CD8(+) T cells and their secreted cytokines in the pathogenesis of AA.
Anemia, Aplastic ; immunology ; metabolism ; pathology ; CD8-Positive T-Lymphocytes ; immunology ; metabolism ; secretion ; Cytokines ; metabolism ; Humans ; Immunity, Cellular

OBJECTIVETo measure the subsets of dendritic cells 1 (DC1) in the bone marrow of severe aplastic anemia (SAA) patients and evaluate the relationships between the CD11c+CD83+ cells and Th1 cells, CD3+CD8+ cells or hematopoietic function and explore the role of DC1 in the pathogenesis of SAA.

METHODSBy FACS, the quantities and ratios of CD11c+CD1a+ cells, CD11c+CD83+ cells, Th1 cells, and CD3+CD8+ cells in the bone marrow of SAA patients and normal controls were detected respectively. The relationships between CD3+CD8+ cells and reticulocyte absolute value (Ret) or neutrophil absolute value (ANC), between Th1 cells and CD3+CD8+ cells, Ret or ANC, between CD11c+CD83+ cells, and Th1 cells, CD3+CD8+ cells, Ret or ANC were evaluated.

RESULTSIn normal controls' bone marrow, the percentages of Th1 cells, CD11c+CD1a+ cells, CD11c+CD83+ cells and the ratio of CD11c+CD83+/CD11c+CD1a+ were (0.42 +/- 0.30)%, (0.38 +/- 0.29)%, (0.37 +/- 0.32)% and 1.07 +/- 0.10, respectively. In untreated SAA patients, they were (4.87 +/- 0.54)%, (1.73 +/- 0.24)%, (3.38 +/- 0.56)% and 2.21 +/- 0.32 respectively, which were higher than that in normal controls (P < 0.01). In recovering SAA patients, the percentages of Th1 cells, CD11c+CD1a+ cells and CD11c+CD83+ cells decreased significantly to (0.53 +/- 0.22)%, (0.61 +/- 0.23)%, (0.65 +/- 0.22)%, respectively (P < 0.01). The ratio of CD11c+CD83+/CD11c+ CD1a+ in recovering SAA patients decreased to 1.37 +/- 0.25, which was similar to that in normal controls (P > 0.05). The percentage of CD3+CD8+ cells in untreated SAA patients was (32.32 +/- 10.22)%, and in recovering SAA patients decreased to (13.67 +/- 5.24)% (P < 0.01). The percentage of CD3+CD8+ cells in SAA patients was negatively correlated with their Ret and ANC (P < 0.05), while their Th1 cell percentages were positively correlated with their CD3+CD8+ cells (P < 0.01), and negatively correlated with their Ret and ANC (P < 0.01). SAA patient's CD11c+CD83+ cell percentages were positively correlated with their Th1 cell and CD3+CD8 cells (P < 0.01, P < 0.05), but negatively with their Ret and ANC (P < 0.01).

CONCLUSIONBoth immature DC1 and activated DC1 increased in the bone marrow of SAA patients, and the balance of DC1 subsets shifted from stable form to active one, which might promote Th0 cells to polarize to Th1 cells, and cause the over-function of T lymphocytes and hematopoiesis failure in SAA.

Adolescent ; Adult ; Anemia, Aplastic ; immunology ; Antigens, CD ; immunology ; Antigens, CD1 ; immunology ; Bone Marrow ; immunology ; CD11c Antigen ; immunology ; CD8-Positive T-Lymphocytes ; immunology ; Child ; Dendritic Cells ; immunology ; Female ; Humans ; Immunoglobulins ; immunology ; Male ; Membrane Glycoproteins ; immunology ; Th1 Cells ; immunology ; Young Adult