Activated and Memory T Lymphocytes in Children with Gaucher Disease

Abstract

Gaucher disease (GD) is the most prevalent lysosomal storage disorder. Gaucher disease is associated with remarkable alterations in the immune system, and GD patients are more susceptible to infections and are at a higher risk of developing autoimmune disorders and malignancies. In a case-control study, we used three-color flow cytometric immunophenotyping for determination of the frequency of lymphocyte subpopulations and activated T lymphocytes among 18 children with GD1 under enzyme replacement therapy managed in Assiut University Hospitals. We found significant increases in the frequencies of total lymphocytes, CD19, CD3, CD4, and CD8 in children with GD1 when compared to healthy control. The frequencies of activated T lymphocytes (CD3HLA-DR), activated T-helper cells (CD4HLA-DR), and activated T-suppressor/cytotoxic cells (CD8HLA-DR) were significantly higher in GD1 as compared to healthy children. Our data show that the increased proportion of activated T lymphocytes in children with GD1 raises the issue of their possible involvement in the pathogenesis of the immune dysfunction seen in these patients. Our data suggested that the activated T lymphocytes could play a role in the clinical course of GD1. The relationship of these cells to immune disorders in GD1 children remains to be determined.

Glycosphingolipids and neuroinflammation in Parkinson’s disease

“…Also, Zahran and colleagues used three-color flow cytometric immunophenotyping for determination of the frequency of lymphocyte subpopulations and activated T lymphocytes in the peripheral blood among eighteen children with Gaucher disease type 1. They showed increases in the frequencies of activated T lymphocytes (CD3+HLA-DR+ ), activated T-helper cells (CD4+HLA-DR+) and activated T-suppressor/cytotoxic cells (CD8+HLA-DR+) in Gaucher disease type 1 as compared to healthy children [110]. Shoenfeld and coworkers demonstrated a significant increase in the incidence of autoantibodies against 14 autoantigens in the sera of 43 patients with Gaucher disease, ranging from 11% for anti-ribonucleoprotein, anti-pyruvate dehydrogenase and anti-DNA antibodies to 57% for rheumatoid factor [111].…”

C-X-C Motif Chemokine Ligand 9 and Its CXCR3 Receptor Are the Salt and Pepper for T Cells Trafficking in a Mouse Model of Gaucher Disease

“…CD8 + T cells are important for inducing autoimmune and the anti-cancer and anti-viral responses [ 37 , 38 , 39 , 40 ]. T cell defects, T cell lymphomas, and increased incidence of CD3 + , CD4 + , CD8 + , CD3 + HLA-DR + , CD4 + HLA-DR + , and CD8 + HLA-DR + subset of activated T cells have been observed in lung and peripheral blood of patients with GD [ 41 , 42 , 43 , 44 , 45 , 46 ]. Significantly elevated levels of CD4 + T cells and modest changes in CD8 + T cells were present in liver, lung, spleen, and thymus of Gba1 9V/− mice [ 5 , 6 , 47 ].…”

“…IFNγ drives increased expression of CXCR3 and its ligands, (e.g., CXCL9–11) that are increased in several inflammatory diseases [ 64 , 65 , 66 , 67 , 68 , 69 , 70 ]. Elevated levels of IFNγ and CXCL9–11 as well as increased numbers of tissue T cells were found in GD mouse models and human patients with GD [ 5 , 6 , 15 , 41 , 42 , 43 , 44 , 45 , 47 , 71 ]. However, the cellular mechanism(s) that causes increased tissue recruitment of T cells in Gba1 9V/− mice is unclear.…”

Down-regulation of Regulatory T-cells in Children With Gaucher Disease Under Enzyme Replacement Therapy

“…Gaucher disease (GD) is a lysosomal storage disease caused by the deficiency of glucocerebrosidase enzyme, leading to the accumulation of undigested glucosylceramide in the reticuloendothelial system cells mainly the macrophages (Gaucher cells), which accumulate in different organs mainly bone marrow, spleen, and liver giving the disease its distinct clinical picture. 1 Although less common, the heart, lungs, and kidneys may be infiltrated by Gaucher cells. 2,3 T-lymphocytes perform and regulate many of the immune processes and play a major role in immune homeostasis.…”

“…It is still not fully known how GD leads to the altered biochemical and immunological cellular functions observed in the disease. [1][2][3] Previous studies have shown a significant reduction in CD4 þ , Tgd2, and natural killer (NK) T-cells and a significant increase in CD4 þ memory cells. While other studies have confirmed decreased numbers of CD4 þ and CD8 þ , others have found an increase in CD8 þ and a decrease in CD4 þ , which was independent of whether patients received enzyme replacement therapy (ERT) or not.…”