Impaired T-Lymphocyte Subpopulations and Deranged Profile of Immunologic Activation in Patients with Gaucher Disease Type I

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4915-4915
Author(s):  
Argiris S Symeonidis ◽  
George Theodorou ◽  
Constantina Repa ◽  
Theodore Marinakis ◽  
Panayiotis Tsaftaridis ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Gaucher Disease ◽  
Lymphocyte Activation ◽  
Absolute Number ◽  
Lymphocyte Subpopulations ◽  
Type I ◽  
Cd8 T Lymphocytes ◽  
T Lymphocyte Subpopulations ◽  
Hla Dr

Abstract Patients with Gaucher disease exhibit substantial evidence of impairment of their immune system, namely, increased serum levels of proinflammatory cytokines and immunoglobulins, and increased incidence of B-cell malignancies, such as non-Hodgkin’s lymphoma, MGUS and multiple myeloma. We investigated peripheral blood T-lymphocyte subpopulations with dual color flow cytometry, as well as the direction of T-lymphocyte activation, by using intracytoplasmic immunostaining for IL-2, IL-4, IL-10 and IFN-gamma, on resting CD4+ and CD8+ T-lymphocytes and following activation with PMA- 1 with the presence of Brefeldin-A. Evaluations were performed on 16 patients with type I Gaucher disease and on 17 healthy controls. Patients had significantly decreased absolute lymphocyte count (1621±684 vs 2148±566/mm3, p=0.013), CD3+ (1197±478 vs 1508±431/mm3, p=0.045) and CD4+ T-lymphocytes (658±245 vs 945±253/mm3, p=0.021), but not CD8+ T-lymphocytes (491±331 vs 486±189/mm3, p: n.s.), resulting in a significant reduction of the CD4/CD8 ratio (1.59±0.68 vs 2.16±0.83, p=0.041). The populations of naive CD4+CD45RA+ and of memory CD4+CD45RO+ T-lymphocytes were also significantly decreased (218±128 vs 432±179/mm3, p=0.0005 and 484±185 vs 631±231/mm3, p=0.056 respectively), however, CD8+CD45RA+ and CD8+CD45RO+ subpopulations did nor differ significantly, when compared to controls. CD3−CD56+, but not CD3+CD56+ lymphocytes were also decreased (131±82 vs 199±97/mm3, p=0.037). Patients had higher percentages of CD8+ (29.2±9.7 vs 23.5±6.8%, p=0.042), CD8+CD45RA+ (22.1±6.2 vs 18.3±5.0%, p=0.046) and CD8+CD45RO+ T-lymphocytes (13.2±6.2 vs 9.6±3.7%, p=0.027), as well as of activated CD8+HLA-DR+ (0.93±0.68 vs 0.48±0.21%, p=0.008) and CD4+HLA-DR+ T-lymphocytes (1.77±0.93 vs 1.09±0.48%, p=0.008). Moreover, although both, the absolute number and the percentage of CD20+ B-lymphocytes were similar, patients exhibited significantly increased absolute number and percentage of CD5+CD20+ B-lymphocytes (1.63±0.55 vs 0.64±0.37% p=0.00002 and 29±20 vs 13±8/mm3, p=0.011, respectively). Finally, patients with Gaucher disease had significantly increased resting TH2-polarized CD4+T-lymphocytes (CD4+IL-10+: 0.41±0.29 vs 0.24±0.11%, p=0.045) and TH1-polarized CD8+ T-lymphocytes (CD8+IFNγ+: 0.15±0.07 vs 0.08±0.04%, p=0.005, CD8+IL10+: 0.22±0.08 vs 0.32±0.014, p=0.052, and IFNγ+/IL4+ ratio among the CD8+ population 2.54±2.1 vs 1.08±0.91, p=0.018). Following mitogenic activation a very significant impairment of obtaining the TH1 phenotype was observed (CD4+IL2+ lymphocytes 33.7±17.1 vs 65.4±6.1%, p<0.00001). The above findings suggest that in patients with Gaucher disease there is a significant numerical impairment of T-helper lymphocytes and a shift towards TH-2 direction of lymphocyte activation. These findings may explain the rarity of autoimmune manifestations despite the chronic inflammatory reaction, as well as the increased incidence of lymphoid malignancies, which has been reported among patients suffering from this disease.

Purified CD4 T Lymphocyte Infusion Can Result in Graft-Versus-Leukemia Reactivity without Gvhd by Recognition of Broadly Expressed Minor Histocompatibility Antigens in HLA Class-II

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4116-4116
Author(s):  
P. van Balen ◽  
C.A.M. van Bergen ◽  
I. Jedema ◽  
S.A.P. van Luxemburg-Heijs ◽  
J.C. Harskamp ◽  
...  
Keyword(s):  
Immune Response ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Hematopoietic Cells ◽  
Hla Class I ◽  
Class Ii ◽  
Hla Class Ii ◽  
Inflammatory Conditions ◽  
Cd8 T Lymphocytes ◽  
Hla Dr

Abstract Abstract 4116 Donor lymphocyte infusion (DLI) after allogeneic stem cell transplantation (alloSCT) can mediate curative Graft-versus-Leukemia (GVL) reactivity although frequently at the cost of Graft-versus-Host Disease (GVHD). We previously illustrated that donor CD8 T lymphocytes recognizing HLA class-I restricted minor histocompatibility antigens (MiHAs) that are broadly expressed on tissues of the recipient cause GVL associated with GVHD, whereas T lymphocytes recognizing MiHAs selectively expressed on hematopoietic cells, including the malignant cells, can selectively mediate GVL without GVHD. Since in contrast to HLA class-I, expression of HLA class-II molecules is predominantly restricted to hematopoietic cells, we hypothesized that infused purified donor CD4 T lymphocytes may selectively recognize and eliminate hematopoietic cells from the recipient resulting in GVL without GVHD. We treated a patient with CML in blastic phase in remission after intensive chemotherapy with T cell depleted alloSCT from his HLA-identical sibling donor after myelo-ablative conditioning. After donor engraftment, recipient hematopoiesis reoccurred within 3 months to 90% of CD8 T lymphocytes, 13% of CD4 T lymphocytes and 5% of myelopoiesis. As part of a clinical trial, the patient was treated with 106/kg positively selected purified donor derived CD4 T lymphocytes resulting within 19 weeks in conversion into full donor chimerism in all hematopoietic cell lineages in the total absence of GVHD. To characterize the nature of this hematopoiesis restricted immune response, in vivo activated HLA-DR positive CD4 and CD8 T lymphocytes were clonally isolated by flowcytometric cell sorting at the time of the clinical response, expanded and tested for alloreactivity on patient and donor derived hematopoietic target cells using IFNγ ELISA. From the 204 expanding CD4 T lymphocyte clones 31 clones were alloreactive, whereas none of the 66 expanding CD8 T lymphocyte clones showed alloreactivity. To further identify the fine specificity of this hematopoiesis directed HLA class-II restricted immune response, target molecules of several T lymphocyte clones were molecularly characterized using whole genome association scanning. We first performed blocking studies with HLA class-II restricted monoclonal antibodies and identified HLA-DR to be the restriction molecule. Next, a large panel of third party EBV-LCLs was retrovirally transduced with each of the possible restriction molecules being HLA-DRB1*11:01, HLA-DRB1*15:01, HLA-DRB3*02:02 and HLA-DRB5*01:01. By comparing the recognition pattern of the transduced EBV-LCLs with the 1.1 million single nucleotide polymorphisms in each EBV-LCL, we identified 3 novel MiHAs. Synthesis and analysis of the patient and donor derived allelic peptide variants further confirmed the specificity of the MiHAs as LB-KHNYN-1K in the context of HLA-DRB5*01:01, LB-CTSB-1G in HLA-DRB1*11:01 and LB-ZDHHC13-1K in HLA-DRB1*15:01. Gene expression profiles of KHNYN (located on chromosome 14), CTSB (chromosome 8) and ZDHHC13 (chromosome 11) illustrated that the genes encoding these MiHAs were not only transcribed in hematopoietic cells, but also in other tissues including GVHD target tissues. These results further illustrated that the hematopoietic specificity of the CD4 T lymphocyte response was mainly defined by the restricted expression of the HLA-DR molecules on hematopoietic cells. We conclude that purified CD4 DLI can lead to GVL without GVHD by a selective HLA class-II restricted immune response against patient hematopoiesis. By molecular characterization of 3 novel HLA-DR restricted MiHAs we illustrated that the relative specificity of HLA class-II molecules on hematopoietic cells under non inflammatory conditions was probably responsible for this effect. Since HLA class-II is predominantly expressed on hematopoietic cells only, infusion of donor CD4 T lymphocytes under non inflammatory conditions after HLA identical alloSCT can result in efficient induction of GVL without the toxicity of GVHD. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Hydrogen peroxide promotes the activation of preeclampsia peripheral T cells

2018 ◽  
Vol 24 (4) ◽  
pp. 203-209 ◽  
Author(s):  
Jingzhu Lv ◽  
Xiaojie Zhang ◽  
Caizhi Wang ◽  
Hongtao Wang ◽  
Ting Wang ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Immune Activation ◽  
Lymphocyte Activation ◽  
Neutrophil Granulocytes ◽  
T Lymphocyte Activation ◽  
Hla Dr ◽  
Intracellular Ros ◽  
Oxidative Stress Status ◽  
High Oxidative Stress

Preeclampsia (PE) is a pregnancy disorder with a high mortality rate. Patients with PE exhibit systemic high oxidative stress status and inflammatory immune activation. This study aims to define the role of H2O2 in the activation of neutrophils and T lymphocytes in PE patients. CD3+/HLA-DR+ cells in blood from PE patients are remarkably increased compared with those of normal non-pregnancies or normal pregnancies, while the percentage of CD3+/CD62L+ cells is significantly reduced in PE patients compared to normal pregnancies. Furthermore, CD62L levels in granulocytes of periphery blood of PE patients are significantly higher than non-pregnancies, but significantly lower than normal pregnancies. To characterize the effects of intracellular reactive oxygen species (ROS) on T lymphocyte activation in PE patients, PBMCs from normal pregnancies were challenged with H2O2, and intracellular ROS levels in neutrophil granulocytes, as well as T cell surface marker levels, have been determined. We confirm that H2O2 exposure increases intracellular ROS levels in neutrophil granulocytes, and increases the proportion of CD3+/HLA-DR+ cells, but does not alter the percentage of CD3+/CD62L+ cells in PBMCs. Our study has confirmed dysregulated CD3+/HLA-DR+ and CD3+/CD62L+ T lymphocytes in PE patient peripheral blood, and the dysregulative effects of H2O2 on T lymphocyte activation, suggesting a novel mechanism of immune activation in PE.

scholarly journals The immunosuppressive effects of volatile versus intravenous anesthesia combined with epidural analgesia on kidney cancer: a pilot randomized controlled trial

2020 ◽  
Vol 73 (6) ◽  
pp. 525-533
Author(s):  
Sergey Mihailovich Efremov ◽  
Victoria Sergeevna Kozireva ◽  
Gleb Borisovich Moroz ◽  
Marat Nikolaevich Abubakirov ◽  
Olga Sergeevna Shkoda ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Epidural Analgesia ◽  
Kidney Cancer ◽  
T Lymphocyte ◽  
Lymphocyte Subpopulations ◽  
Cell Mediated Immunity ◽  
Inhalational Anesthesia ◽  
Intravenous Anesthesia ◽  
Thoracic Epidural ◽  
T Lymphocyte Subpopulations

Background: The aim of this study was to test the hypothesis that the use of inhalational anesthesia leads to higher suppression of the cell-mediated immunity compared to total intravenous anesthesia in patients undergoing kidney cancer surgery under combined low thoracic epidural analgesia and general anesthesia. Methods: Patients were randomly allocated to either propofol-based (intravenous anesthetic) or sevoflurane-based (volatile anesthetic) anesthesia group with 10 patients in each group, along with epidural analgesia in both groups. Amounts of natural killer cells, total T lymphocytes, and T lymphocyte subpopulations in the blood samples collected from the patients before surgery, at the end of the surgery and postoperative days 1, 3, and 7, were determined by flow cytometric analysis. The natural killer (NK) cell count served as the primary endpoint of the study, whereas the total T lymphocyte count and cell counts for T lymphocyte subpopulations were used as the secondary endpoint. . Results: Our study showed that there were no significant differences in the amount of NK cells, total T lymphocytes, regulatory T cells, and T-helper cells, cytotoxic T lymphocytes, and their subpopulations between the propofol- and sevoflurane-based anesthesia groups when the anesthesia was administered in combination with epidural analgesia. Conclusions: The results of this pilot study did not support the hypothesis that the use of inhalational anesthesia leads to higher suppression of the cell-mediated immunity than that of total intravenous anesthesia in patients undergoing kidney cancer surgery under combined low thoracic epidural analgesia and general anesthesia.

scholarly journals Causes of T lymphocyte activation in HIV-infected patients coinfected with hepatitis C virus

2016 ◽  
Vol 88 (11) ◽  
pp. 22-28
Author(s):  
K V Shmagel ◽  
N G Shmagel ◽  
L B Korolevskaya ◽  
E V Saydakova ◽  
V A Chereshnev
Keyword(s):  
T Cells ◽  
Hepatitis C ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Activation ◽  
T Lymphocyte ◽  
Cell Activation ◽  
Lymphocyte Activation ◽  
Cd8 T Cell ◽  
Cd8 T Lymphocytes

Aim. To establish the causes of T lymphocyte activation in human immunodeficiency virus (HIV)-infected patients coinfected with hepatitis C (HCV) who are adherent to their antiretroviral therapy regimen and interferon untreated. Subjects and methods. Examinations were made in 62 people who were HIV+HCV-positive (n=21), HIV+HCV-negative (n=21), and noninfected volunteers (n=20). The activation (CD38+HLA-DR+) and proliferation (Ki-67+) of CD4+ and CD8+ T lymphocytes were estimated. The blood concentration of intestinal fatty acid-binding protein (I-FABP) was determined. Results. The proportion of activated cells among the CD4+ T lymphocytes was equal in the HIV+HCV-positive and HIV+HCV-negative groups. But these indicators were statistically significantly higher than those in the controls (HIV- HCV-). CD8+ T cell activation was greater in the HIV/HCV-coinfected patients than that in the other groups and that was higher in the HIV monoinfected than in the noninfected. The blood I-FABP concentrations were elevated in the HIV+HCV-positive and HIV+HCV groups compared with those in the HIV-HCV-negative group, but these did not differ among themselves. In the HIV+HCV-negative patients, CD4+ and CD8+ T cell activation directly and statistically significantly correlated with blood I-FABP levels. In the HIV+HCV-positive group, this correlation remained only for CD4+ T lymphocytes. CD8+ T cell activation in HIV/HCV-coinfected patients was unrelated to I-FABP concentrations. Conclusion. The increased activation of CD4+ and CD8+ T lymphocytes in HIV monoinfection was found to be associated with intestinal epithelial destruction and unrelated to cell division processes. In HIV/HCV coinfection, the activated state of CD4+ T cells is determined by both the level of proliferative processes and impairment of the intestinal barrier and that of CD8+ T cells is only by proliferation.

Effect of Qigong Training on Proportions of T Lymphocyte Subsets in Human Peripheral Blood

1995 ◽  
Vol 23 (01) ◽  
pp. 27-36 ◽  
Author(s):  
Hoon Ryu ◽  
Chang Duk Jun ◽  
Bok Soo Lee ◽  
Byung Min Choi ◽  
Hyung Min Kim ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Peripheral Blood ◽  
Lymphocyte Subsets ◽  
Human Peripheral Blood ◽  
Absolute Number ◽  
T Lymphocyte Subsets ◽  
Healthy Group ◽  
Cd8 T Lymphocytes ◽  
Trainee Group

The effect of Qigong training on proportions of T lymphocyte subsets was investigated in human peripheral blood. We observed that the ratio of CD4+/CD8+ T lymphocytes was increased as much as 50% in a trainee group who practiced Qigong training more than 5 months compared to a normal healthy group who did not practice. The absolute number of CD4+ T lymphocytes was also elevated in trainee group with 100 cells/mm 3 more than in normal healthy group. The positive correlation between the ratio of CD4+/CD8+ T lymphocytes and the ratio of CD4+45RA-/CD4+ CD45RA+ T lymphocytes was shown in the trainee group. In contrast, there was a negative correlation between the ratio of CD4+/CD8+ T lymphocytes and the ratio of CD8+CD57+/CD8+CD57- T lymphocytes in the trainee group. The data indicate that Qigong training affects the profile of lymphocyte subsets in human peripheral blood, especially the proportion of CD4+ T lymphocytes.

Alterations in T-Lymphocyte Subpopulations in Type I Diabetes: Exploration of Genetic Influence in Identical Twins

Diabetes ◽  
1988 ◽  
Vol 37 (11) ◽  
pp. 1484-1488 ◽  
Author(s):  
C. Johnston ◽  
L. Alviggi ◽  
B. A. Millward ◽  
R. David ◽  
G. Leslie ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Type I Diabetes ◽  
Lymphocyte Subpopulations ◽  
Genetic Influence ◽  
Identical Twins ◽  
Type I ◽  
T Lymphocyte Subpopulations

Alterations in T-lymphocyte subpopulations in type I diabetes. Exploration of genetic influence in identical twins

Diabetes ◽  
1988 ◽  
Vol 37 (11) ◽  
pp. 1484-1488 ◽  
Author(s):  
C. Johnston ◽  
L. Alviggi ◽  
B. A. Millward ◽  
R. D. Leslie ◽  
D. A. Pyke ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Type I Diabetes ◽  
Lymphocyte Subpopulations ◽  
Genetic Influence ◽  
Identical Twins ◽  
Type I ◽  
T Lymphocyte Subpopulations

scholarly journals Level of CD8 T Lymphocytes Activation in HIV-Infected Pregnant Women: In the Context of CD38 and HLA-DR Activation Markers

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Stanslaus Musyoki ◽  
Simeon Mining ◽  
Paul Nyongesa
Keyword(s):  
T Lymphocytes ◽  
Pregnant Women ◽  
T Lymphocyte ◽  
Immune Activation ◽  
Hiv Positive ◽  
Cd8 T Lymphocytes ◽  
Cd8 T Lymphocyte ◽  
Hla Dr ◽  
Study Results ◽  
Study Participants

Background. To date the effect of pregnancy on the immune activation of CD8 T cells that may affect HIV disease progression has not been well studied and remains unclear.Objective.To determine the effect of pregnancy on CD8 T lymphocyte activation and its relationship with CD4 count in HIV infected pregnant women.Study Design. Case control.Study Site. AMPATH and MTRH in Eldoret, Kenya.Study Subjects. Newly diagnosed asymptomatic HIV positive pregnant and nonpregnant women with no prior receipt of antiretroviral medications.Study Methods. Blood samples were collected from the study participants and levels of activated CD8 T lymphocytes (CD38 and HLA-DR) were determined using flow cytometer and correlated with CD4 counts of the study participants. The descriptive data focusing on frequencies, correlation, and cross-tabulations was statistically determined. Significance of the results was set atP<0.05.Results. HIV positive pregnant women had lower activated CD8 T lymphocyte counts than nonpregnant HIV positive women. Activated CD8 T lymphocyte counts were also noted to decrease in the second and third trimesters of pregnancy.Conclusion. Pregnancy has a significant suppression on CD8+ T lymphocyte immune activation during HIV infections. Follow-up studies with more control arms could confirm the present study results.

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