CD4+CD25highCD127low/-FoxP3 + Regulatory T-Cell Population in Acute Leukemias: A Review of the Literature.

Regulatory T-cells (Tregs) are a very important subtype of lymphocytes when it comes to self-control in the human immunological system. Tregs are decisive not only in the protection against destruction of own tissues by autoimmune immunocompetent cells but also in the immunological answer to developing cancers. On the other hand, Tregs could be responsible for the progression of acute and chronic leukemias. In our study, we review publications available in the PUMED database concerning acute leukemia, with a particular emphasis on child's leukemias. The percentage of regulatory T-lymphocytes in peripheral blood and bone marrow was elevated compared to those in healthy individuals and correlated with progressive disease. Regulatory T-cells taken from children diagnosed with leukemia showed a higher suppressive capability, which was confirmed by detecting elevated levels of secreted IL-10 and TGF-beta. The possibility of pharmacological intervention in the self-control of the immunological system is now under extensive investigation in many human cancers. Presumably, Treg cells could be a vital part of targeted therapies. Routine Treg determination could be used to assess the severity of disease and prognosis in children with acute lymphoblastic leukemia. This proposition results from the fact that in some studies, higher percentage of Treg cells in peripheral blood was demonstrated. However, observations confirming these facts are scarce; thus, extrapolating them to the population of children with hematological malignancies needs to be verified in additional studies.

CD4+CD25highCD127low/-FoxP3+ Regulatory T Cell Subpopulations in the Bone Marrow and Peripheral Blood of Children with ALL: Brief Report.

CD4+CD25highCD127low/-FoxP3+ regulatory T cells (Tregs) are currently under extensive investigation in childhood acute lymphoblastic leukemia (ALL) and in other human cancers. Usually, Treg cells maintain the immune cell homeostasis. This small subset of T cells has been, in fact, considered to be involved in the pathogenesis of autoimmune diseases and progression of acute and chronic leukemias. However, whether Treg dysregulation in CLL and ALL plays a key role or it rather represents a simple epiphenomenon is still a matter of debate. Treg cells have been proposed as a prognostic indicator of the clinical course of the disease and might also be used for targeted immune therapy. Our study revealed statistically higher percentage of Treg cells in the bone marrow than in peripheral blood in the group of 42 children with acute lymphoblastic leukemia. By analyzing Treg subpopulations, it was shown that only memory Tregs in contact with leukemic antigens showed statistically significant differences. We noticed a low negative correlation between Treg cells in the bone marrow and the percentage of blasts (R = -0.36) as well as a moderate correlation between Treg cells in the bone marrow and Hb level (R = +0.41) in peripheral blood before therapy. The number of peripheral blood blasts on day 8th correlates negatively (R = -0.36) with Tregs. Furthermore, statistical analysis revealed low negative correlation between the number of Tregs in the bone marrow and the minimal residual disease measured on day 15th, the percentage of blasts in the bone marrow and leukocytosis after 15 days of chemotherapy. These results indicate the influence of Tregs on the final therapeutic effect.

Impairment of Immune Function in Children with Familial Hemophagocytic Lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a severe systemic syndrome associated with hyperactivation of macrophages and impaired regulation of the immune system. Two forms of HLH are currently recognized: genetically determined or familial (FHLH), and secondarily developed in the course of primary diseases, like autoimmune disorders, rheumatoid disorders, cancers, or infections. In the Polish population, FHLH is rather rare. The aim of the present study was to assess the immune function in a group of children with clinical symptoms suggesting FHLH. Forty five children with suspected HLH of the median age of 4 years and 15 healthy children, taken as a control group, were enrolled into the study. All presented results were obtained with the use of flow cytometry. In the HLH group, there were only three cases identified with the UNC13D gene mutation responsible for the FHLH3 phenotype. Another four children, without known mutation, were classified as FHLH because of frequent recurrence of the disease. In all cases of FHLH, cell cytotoxicity was impaired compared with healthy children (p = 0.003). Perforin expression in FHLH was normal or higher than that observed in controls (p = 0.09). In case of patients with mutation in the Munc13 protein, degranulation was lower than that in healthy children (<5 %). The findings of this study demonstrate that children with known mutations responsible for the FHLH development are immunocompromised. However, it requires further elucidation whether the presence of currently unknown mutations could lead to a similar phenotype.