Immunomodulatory Influence by Interferon alpha and Imatinib Mesylate in Chronic Myeloid Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4534-4534
Author(s):  
Kazuaki Yokoyama ◽  
Tokiko Nagamura-Inoue ◽  
Shin Nakayama ◽  
Ikuo Ishige ◽  
Nobuhiro Ohno ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chronic Myeloid Leukemia ◽  
T Cell Activation ◽  
Myeloid Leukemia ◽  
Cell Activation ◽  
Cell Function ◽  
Control Group ◽  
Immunological Parameters

Abstract Objectives: Imatinib mesylate (STI) is the first-line therapy for chronic myeloid leukemia in the chronic phase (CML-CP). However, STI as well as interferonα (IFN) has been reported to inhibit both T-cell activation and B cell function. To clarify the immunological differences by the type of therapy, we compared immunological parameters between CML patients in very good CyR to either STI or IFN as well as normal volunteers. We also studied the in vitro effects of STI on immune cell function. Patients and Methods: Each group comprised 14 subjects. The median treatment dose and duration were 6 MIU/week and 174 months for IFN, and 400 mg/day and 54 months for STI, respectively. Peripheral blood sample was used and subjected to multi-color flow cytometry (FCM) acquisition and analysis. For analysing TCR-mediated activation of T cells, we stained MNC with CFSE and stimulated those with anti-CD3/CD28 antibodies in the presence of STI at various concentrations for 4 days, followed by FCM. Results: The summary is shown in Table. WBC counts were well controlled at moderately lower levels than in the control group of normal volunteers: Hb levels were significantly reduced in the STI-group compared to the other two groups (P<0.0001), while platelet counts were lower in the IFN-group than in the control group (P<0.01). The number of T cells was significantly lower in both patient groups (P=0.0006), while the NK cell number was comparable among the three groups. Not only the absolute numbers of monocytes and B cells but also serum IgG and IgA titers were significantly lower in the STI- than IFN-group (P<0.0001). For T-cell subsets, the ratio of CD4/8 T cells was significantly lower, but that of CD26highCD4+ T cells was significantly higher in the IFN- than STI-group. TCR-triggered T cell proliferation was suppressed by STI in a dose dependent manner. Intriguingly, we also found that STI treatment resulted in significant down-regulation of CD4+CD26high T cell population which is considered as a subset of effector T cells. Collectively, our data imply that the two therapeutic agents induce a distinct immunological status in CML patients, and also raise the possibility that immunological surveillance of residual Ph clone may be somewhat defective in patients receiving STI for prolonged periods. In addition, STI revealed the inhibitory effect on TCR-mediated T cell activation in vitro. Finally, the periodic monitoring of immunological parameters is recommended for these patients. Control IFN STI No.of Subjects 14 14 14 Median age (range) 41 (30–63) 50 (39–73) 54 (29–65) Immune parameters Mean (SD) p value WBC (10^9/L) 5.50 (1.21) 4.81 (1.36) 3.95 (0.89) .0056 T cells (10^9/L) 1.02 (0.22) 0.63 (0.28) 0.59 (0.28) .0006 CD26high/CD4+T cells (%) 9.12 (5.19) 12.08 (5.01) 7.92 (3.65) .0407 Monocytes (10^8/L) 2.81 (0.53) 3.56 (1.52) 1.87 (1.10) .0003 B cells (10^8/L) 2.67 (1.34) 2.61 (1.67) 1.38 (0.94) .0201 Serum IgG (g/L) 15.63 (3.95) 10.32 (2.10) <.0001 Serum IgA (g/L) 3.70 (0.24) 2.32 (0.24) .0013

scholarly journals TRPM2 Is Not Required for T-Cell Activation and Differentiation

2022 ◽  
Vol 12 ◽  
Author(s):  
Niels C. Lory ◽  
Mikolaj Nawrocki ◽  
Martina Corazza ◽  
Joanna Schmid ◽  
Valéa Schumacher ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Transient Receptor Potential ◽  
Cell Function ◽  
Intestinal Inflammation ◽  
Activation Markers

Antigen recognition by the T-cell receptor induces a cytosolic Ca2+ signal that is crucial for T-cell function. The Ca2+ channel TRPM2 (transient receptor potential cation channel subfamily M member 2) has been shown to facilitate influx of extracellular Ca2+ through the plasma membrane of T cells. Therefore, it was suggested that TRPM2 is involved in T-cell activation and differentiation. However, these results are largely derived from in vitro studies using T-cell lines and non-physiologic means of TRPM2 activation. Thus, the relevance of TRPM2-mediated Ca2+ signaling in T cells remains unclear. Here, we use TRPM2-deficient mice to investigate the function of TRPM2 in T-cell activation and differentiation. In response to TCR stimulation in vitro, Trpm2-/- and WT CD4+ and CD8+ T cells similarly upregulated the early activation markers NUR77, IRF4, and CD69. We also observed regular proliferation of Trpm2-/- CD8+ T cells and unimpaired differentiation of CD4+ T cells into Th1, Th17, and Treg cells under specific polarizing conditions. In vivo, Trpm2-/- and WT CD8+ T cells showed equal specific responses to Listeria monocytogenes after infection of WT and Trpm2-/- mice and after transfer of WT and Trpm2-/- CD8+ T cells into infected recipients. CD4+ T-cell responses were investigated in the model of anti-CD3 mAb-induced intestinal inflammation, which allows analysis of Th1, Th17, Treg, and Tr1-cell differentiation. Here again, we detected similar responses of WT and Trpm2-/- CD4+ T cells. In conclusion, our results argue against a major function of TRPM2 in T-cell activation and differentiation.

Platelets from Patients with Myocardial Infarction Can Activate T Cells in Vitro

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3448-3448 ◽  
Author(s):  
Elena E. Solomou ◽  
Vasilios Gizas ◽  
Theodora Babali ◽  
Angelos Perperis ◽  
Evgenia Verigou ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
T Cells ◽  
T Cell ◽  
Unstable Angina ◽  
T Cell Activation ◽  
Healthy Subjects ◽  
Cell Activation ◽  
Control Group ◽  
Healthy Controls

Abstract Specific aim: Our aim was to examine whether T cells can be activated by the circulating activated platelets from patients with myocardial infarction (with ST elevation-STEMI) Methods: After written informed consent was obtained, peripheral blood mononuclear cells (PBMCs) were isolated from heparinized venous blood obtained from 20 patients with STEMI (18 men and 2 women) at the time of hospital admission at diagnosis, before receiving any treatment, as well as 5 days and 30 days later. We also analyzed 10 healthy subjects (8 men and 2 women), and 5 patients with unstable angina who served as the disease control group. PBMCs were analyzed by flow cytometry with the following markers and their isotypic controls: CD4, CD25, CD69, and FOXP3. We also isolated platelet rich plasma or plasma alone from the patients and the healthy subjects, and used in mixed cultures with PBMCs. Results: We first examined T cell activation by measuring CD69 expression on CD4 T cells following incubation with platelets obtained from patients with STEMI. T cells treated with platelets from patients with STEMI showed increased expression of CD69 (as an activation marker) compared with T cells treated with platelets from healthy subjects (p<0.05, Figure 1). There was no T cell activation following incubation with plasma alone from patients or healthy controls. We then examined the percentages of CD4+CD25+hi (regulatory T cells). There was no statistical difference in Tregs between patients at presentation and controls (healthy subjects and disease control group). Five days later, patients with STEMI displayed increased levels of Tregs compared with the 2 control groups; one month later, Treg numbers returned to the initial presentation levels (p<0.05, Figure 2) Conclusion: To our knowledge we describe for the first time that platelets from patients with STEMI can activate T cells in vitro. In patients with STEMI, an increase in Tregs possibly in an effort to suppress immune system activation secondary to platelet activation, appears shortly after the infarct and normalizes a month later. Figure 1. T cell activation after treatment with platelets from patients with STEMI compared with the platelets from healthy controls or plasma alone Figure 1. T cell activation after treatment with platelets from patients with STEMI compared with the platelets from healthy controls or plasma alone Figure 2. Increased T regs in patients with STEMI , 5 days after admission (STEMI EXIT) ( UA;unstable angina, STEMI 1mfup; STEMI after one month) Figure 2. Increased T regs in patients with STEMI , 5 days after admission (STEMI EXIT) ( UA;unstable angina, STEMI 1mfup; STEMI after one month) Disclosures No relevant conflicts of interest to declare.

scholarly journals Renal tuberculosis in an imatinib-treated chronic myeloid leukemia

2020 ◽  
Vol 42 (3) ◽  
pp. 366-369
Author(s):  
Abhilash Chandra ◽  
Namrata Rao ◽  
Kiran Preet Malhotra
Keyword(s):  
T Cell ◽  
Chronic Myeloid Leukemia ◽  
T Cell Activation ◽  
Myeloid Leukemia ◽  
Cell Activation ◽  
Cell Function ◽  
Standard Form ◽  
Maintenance Phase ◽  
Imatinib Therapy ◽  
Renal Tuberculosis

ABSTRACT Imatinib, which inhibits tyrosine kinase activity of Bcr-Abl protein, is a standard form of treatment for chronic myeloid leukemia (CML). Through its immunomodulatory effect it affects T cell function in a number of ways. It inhibits antigen-induced T cell activation and proliferation. Antigen-specific T-cells and macrophages are vital for protection against Mycobacterium tuberculosis. Here we present a case of renal tuberculosis associated with imatinib therapy in the maintenance phase of CML. With granulomatous interstitial nephritis and positive tubercular DNA on renal biopsy, the condition was successfully treated with anti-tubercular therapy. This case provides support to the hypothesis that imatinib therapy in CML increases the susceptibility to tuberculosis and strict vigilance is required to enable its early detection and treatment.

Rituximab Directly Decreases T Cell Activation, Both In Vivo and In Vitro

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3935-3935 ◽  
Author(s):  
Tamar Katz ◽  
Dina Stroopinsky ◽  
Jacob M. Rowe ◽  
Irit Avivi
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
T Cell Activation ◽  
Inflammatory Cytokine ◽  
Cell Activation ◽  
Cell Function ◽  
Activation Profile

Abstract Abstract 3935 Rituximab, a chimeric anti-C20 monoclonal antibody, has been extensively used over the last decade for the therapy of B cell malignancies. Recent clinical data suggest that rituximab may affect T cell function, increasing the risk of T cell dependent infections in heavily-treated patients. The current study was designed to investigate the effect of rituximab on T cell activation and assess T cell function following the addition of rituximab to purified T cells. The T cell activation profile, dependent on rituximab administration, was evaluated in vivo and in vitro. Peripheral blood mononuclear cells (PBMCs) generated from B-cell non-Hodgkin lymphoma (NHL) patients prior and immediately after the administration of 375 mg/m2 rituximab, were examined for the expression of inflammatory cytokines. The in vitro studies were performed by using CD25 depleted PBMCs or B cell depleted T cells (CD3+CD25-CD19-). The obtained cells were stimulated with allogeneic dendritic cells (DCs), in the absence or presence or 2 mg/ml rituximab. T cell activation was evaluated using immunophenotypic markers, cytokine profile and T cell proliferation assay. Eight NHL patients participated in the study. The level of T cells expressing inflammatory cytokines was significantly decreased following the administration of a single dose of rituximab. T cells expressing IL-2 declined from a mean level of 26.5% to 11.5% and the level of IFN- γ decreased from 22% to 4.2%. Further administration of rituximab, up to 4 weekly doses, resulted in an additional decline in the amount of inflammatory cytokine producing T cells to a level of 1.4% for IL-2 and 3.5% for IFN-g. However, repeated evaluation, performed at 4 months after completing rituximab, showed restoration of the inflammatory population. In accord with this inhibitory effect, in vitro stimulation of T cells with allogeneic DCs, in the presence of rituximab, resulted in a significant decrease in activation markers (CD25, GITR and CTLA-4) (Table 1). These changes were accompanied by a marked reduction in inflammatory cytokine production and proliferative capacity. Of interest, these inhibitory effects were also obtained whilst using B cell depleted T cells (CD3+CD25-CD19-). In conclusion, rituximab administration results in a transient T cell inactivation, demonstrated through the reduction in inflammatory cytokine production and T cell proliferation capacity. This effect appears to be non-B cell dependent, being obtained in the absence of B cell in the culture, and may account for clinical observations in ameliorating T-cell dependent disorders, such as graft-versus-host disease. Table 1. Activation profile depending on rituximab (in vitro) Without rituximab With rituximab *Activation marker (%) CD25 27 9 GITR 15.6 4.7 CTLA4 17.7 7 *Cytokines expression (%) IL-2 22 2 IL12 16 4 IFN-gamma 21 1.8 T cells proliferation (O.D.) DC stimulation 1.528 0.580 CMV stimulation 1.563 0.570 anti CD3/CD28 stimulation 0.705 0.407 * Gated out of lymphocytes Disclosures: No relevant conflicts of interest to declare.

scholarly journals Platelet-Induced T Cell Activation in Patients with Myocardial Infarction; The Role of miR155

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4913-4913 ◽  
Author(s):  
Elena E. Solomou ◽  
Elena Kalyvioti ◽  
Evgenia Verigou ◽  
Katerina Katsanaki ◽  
Charalambos Gogos ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
T Cells ◽  
T Cell ◽  
Platelet Activation ◽  
T Cell Activation ◽  
Real Time Pcr ◽  
Healthy Subjects ◽  
Cell Activation ◽  
Control Group

Abstract Specific aim: We have previously shown that platelets from patients with myocardial infarction (with ST elevation-STEMI) can activate T cells in vitro. In this study we wanted to expand our initial observation and explore the mechanism of this T cell activation. Methods: After written informed consent was obtained, peripheral blood mononuclear cells (PBMCs) were isolated from heparinized venous blood obtained from 30 patients with STEMI (28 men and 2 women) at the time of hospital admission at diagnosis, before receiving any treatment, as well as 5 days and 30 days later. We also analyzed 15 healthy subjects (12 men and 3 women), and 7 patients with unstable angina who served as the disease control group. PBMCs were analyzed by flow cytometry with the following markers and their isotypic controls: CD4, CD25, CD127, FOXP3, and CD69. We also isolated platelet rich plasma or plasma alone from the patients and the healthy subjects, and used in mixed cultures with PBMCs. miR 155 levels were examined with real-time PCR. Results: Initially, we incubated T cells with platelets from patients with STEMI and examined T cell activation by CD69 expression. These T cells showed increased expression of CD69 compared to T cells treated with platelets from healthy subjects (p<0.05). No T cell activation was observed following incubation with plasma alone from patients or healthy controls. Next, the percentages of CD4+CD25+hi CD127low FOXP3+ (regulatory T cells, Tregs) were examined in all study subjects. Patients at presentation showed comparable Treg levels with the controls (healthy subjects and disease control group). Five days later, patients with STEMI displayed increased levels of Tregs compared with the controls (p<0.05) (Fig.2). To explore the mechanism of Treg up-regulation the miR155 levels through real time PCR were evaluated. Patients with STEMI showed comparable levels of miR155 at presentation, but five days later showed decreased miR155 levels compared to controls (p<0.001) (Fig. 1); we observed an inverse correlation between miR155 levels and Treg numbers in patients with STEMI. At re-evaluation, one month later, patients with STEMI displayed Treg numbers comparable to the initial presentation levels Conclusion: Herein, we show that platelets from patients with STEMI can activate T cells in vitro. This platelet activation in patients with STEMI, results in an increase in Tregs through down-regulation of miR155, that return to normal levels a month later. This Treg increase reflects possibly an effort to suppress immune system activation secondary to platelet activation, shortly after the infarct. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

scholarly journals A population of CD4+ T cells with a naïve phenotype stably polarized to the TH1 lineage

2020 ◽  
Author(s):  
Jonathan W. Lo ◽  
Maria Vila de Mucha ◽  
Luke B. Roberts ◽  
Natividad Garrido-Mesa ◽  
Arnulf Hertweck ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cell Function ◽  
T Cell Subsets ◽  
T Helper

AbstractT-bet is the lineage-specifying transcription factor for CD4+ T helper type 1 (TH1) cells. T-bet has also been found in other CD4+ T cell subsets, including TH17 cells and TREG, where it modulates their functional characteristics. However, we lack information on when and where T-bet is expressed during T cell differentiation and how this impacts T cell function. To address this, we traced the ontogeny of T-bet-expressing cells using a fluorescent fate-mapping mouse line. We demonstrate that T-bet is expressed in a subset of CD4+ T cells with naïve cell surface markers and that this novel cell population is phenotypically and functionally distinct from conventional naïve CD4+ T cells. These cells are also distinct from previously described populations of memory phenotype and stem cell-like T cells. Naïve-like T-bet-experienced cells are polarised to the TH1 lineage, predisposed to produce IFNγ upon cell activation, and resist repolarisation to other lineages in vitro and in vivo. These results demonstrate that lineage-specifying factors can function to polarise T cells in the absence of canonical markers of T cell activation and that this has an impact on the subsequent T helper response.

scholarly journals Combinatorial Control of Signal-Induced Exon Repression by hnRNP L and PSF

2007 ◽  
Vol 27 (19) ◽  
pp. 6972-6984 ◽  
Author(s):  
Alexis A. Melton ◽  
Jason Jackson ◽  
Jiarong Wang ◽  
Kristen W. Lynch
Keyword(s):  
T Cells ◽  
Alternative Splicing ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cell Function ◽  
Exon Skipping ◽  
Dependent Manner

ABSTRACT Cells can regulate their protein repertoire in response to extracellular stimuli via alternative splicing; however, the mechanisms controlling this process are poorly understood. The CD45 gene undergoes alternative splicing in response to T-cell activation to regulate T-cell function. The ESS1 splicing silencer in CD45 exon 4 confers basal exon skipping in resting T cells through the activity of hnRNP L and confers activation-induced exon skipping in T cells via previously unknown mechanisms. Here we have developed an in vitro splicing assay that recapitulates the signal-induced alternative splicing of CD45 and demonstrate that cellular stimulation leads to two changes to the ESS1-bound splicing regulatory complex. Activation-induced posttranslational modification of hnRNP L correlates with a modest increase in the protein's repressive activity. More importantly, the splicing factor PSF is recruited to the ESS1 complex in an activation-dependent manner and accounts for the majority of the signal-regulated ESS1 activity. The associations of hnRNP L and PSF with the ESS1 complex are largely independent of each other, but together these proteins account for the total signal-regulated change in CD45 splicing observed in vitro and in vivo. Such a combinatorial effect on splicing allows for precise regulation of signal-induced alternative splicing.

scholarly journals A Novel CD34-Specific T-Cell Engager Efficiently Depletes Stem Cells and Acute Myeloid Leukemia Cells in Vitro and In Vivo

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2861-2861
Author(s):  
Lucas C M Arruda ◽  
Liqing Jin ◽  
Melanie Lambert ◽  
Laura Sanchez Rivera ◽  
Renato Alvez ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lines ◽  
T Cell Activation ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Cell Activation ◽  
Privately Held

Abstract ASH Abstract. Intro Acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS) are poor prognosis hematological malignancies characterized by abnormal hematopoiesis and dysfunctions of the hematopoietic stem cell system. Chemotherapy remains the standard of care but is associated with side effects and often high rates of relapse. Today, less than a third of patients diagnosed with AML are cured. Bispecific T-cell engagers (BiTEs) are promising immunotherapeutic agents intended for cancer treatment. BiTEs are small molecules constructed of two single chain variable fragments (scFv) connected in tandem by a flexible linker that acts by retargeting T-cells against tumor cells. One scFv binds to CD3, while the second scFv binds to a tumor-associated antigen. This structure and specificity allow a BiTE construct to physically link a T-cell to a tumor cell, stimulating effector cell activation ultimately leading to cytokine production and tumor killing. Material BiTEs against CD34/CD3 and relevant controls were constructed by recombinant DNA technology and purified from the supernatants of transfected CHO cells following standard procedures. The scFv domain binding to CD34 is positioned N-terminally, and the scFv binding to CD3e C-terminally followed by a hexa-histidine sequence. Results By co-culturing T-cells and target AML cells for 48 h in the presence of increasing concentrations of BiTE or controls, we observed that CD34-BiTE efficiently triggered T-cell-mediated depletion of the CD34 hi and CD34 low cell lines, while negative controls killed none of the target cell lines. Next, we examined the T-cell activation and proliferation. We observed that both CD4+ and CD8+ T-cells presented high levels of CD25/CD69 expressions when the CD34+ cell lines were co-cultured with T-cells in the presence of the CD34/CD3 BiTE. No unspecific activation was found when CD34- cell line was used as target cell. Since CD34 is constitutively expressed by HSCs, the CD34-specific BiTE may deplete not only CD34 +AML blasts but also healthy HSCs. To test this, T-cells and HSCs were purified from PBSC grafts and co-cultured in the presence of either CD34/CD3 BiTE or controls. After co-culture, a significant depletion of CD34 + HSCs was observed for the CD34/CD3 BiTE. To address the potential of the anti-CD34 BiTE in vivo, we next established a human CD34 + cell line in NSG mice per intravenous injection and randomized into three different groups and started treatment the day after. Two groups of mice received two consecutive cycles of one intraperitoneal injection of freshly isolated human T-cells followed by daily intravenous injections of either BiTE or control. The mice were euthanatized at day 21 by which the AML burden was measured, and T-cells quantified. No side effects of the treatment, including after BiTE administration, was observed. There were statistically significant reductions of leukemia burden in both bone marrow and spleen in mice receiving T-cells and BiTE compared to T-cells only and control. Conclusions We show that the CD34/CD3 BiTE is able to promote T-cell activation and killing of CD34-expressing target cells with high efficacy in vitro and in vivo, supporting the translation of this drug into clinical trials. In this scenario, the treatment with CD34-targeting BiTE prior to HSCT would trigger the patient's T-cells to deplete CD34 + leukemic blasts and HSCs. As consequence, this adjuvant treatment would decrease the use of cytotoxic and cytostatic conditioning drugs before HSCT, reducing life-threatening complications such as GvHD and infections. Disclosures Arruda: Anocca: Current Employment, Research Funding. Dick: Celgene, Trillium Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Mattsson: MattssonAB medical: Current Employment, Current holder of individual stocks in a privately-held company. Onfelt: Desumo: Current Employment, Current holder of individual stocks in a privately-held company. Uhlin: XNK therapeutics: Current Employment, Current holder of stock options in a privately-held company.

scholarly journals Immunomodulatory effects of different intravenous immunoglobulin preparations in chronic lymphocytic leukemia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ana Colado ◽  
Esteban Enrique Elías ◽  
Valeria Judith Sarapura Martínez ◽  
Gregorio Cordini ◽  
Pablo Morande ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
T Cell Activation ◽  
Cell Activation ◽  
Lymphocytic Leukemia ◽  
Immunomodulatory Effects ◽  
Immunoglobulin Preparations

AbstractHypogammaglobulinemia is the most frequently observed immune defect in chronic lymphocytic leukemia (CLL). Although CLL patients usually have low serum levels of all isotypes (IgG, IgM and IgA), standard immunoglobulin (Ig) preparations for replacement therapy administrated to these patients contain more than 95% of IgG. Pentaglobin is an Ig preparation of intravenous application (IVIg) enriched with IgM and IgA (IVIgGMA), with the potential benefit to restore the Ig levels of all isotypes. Because IVIg preparations at high doses have well-documented anti-inflammatory and immunomodulatory effects, we aimed to evaluate the capacity of Pentaglobin and a standard IVIg preparation to affect leukemic and T cells from CLL patients. In contrast to standard IVIg, we found that IVIgGMA did not modify T cell activation and had a lower inhibitory effect on T cell proliferation. Regarding the activation of leukemic B cells through BCR, it was similarly reduced by both IVIgGMA and IVIgG. None of these IVIg preparations modified spontaneous apoptosis of T or leukemic B cells. However, the addition of IVIgGMA on in vitro cultures decreased the apoptosis of T cells induced by the BCL-2 inhibitor, venetoclax. Importantly, IVIgGMA did not impair venetoclax-induced apoptosis of leukemic B cells. Overall, our results add new data on the effects of different preparations of IVIg in CLL, and show that the IgM/IgA enriched preparation not only affects relevant mechanisms involved in CLL pathogenesis but also has a particular profile of immunomodulatory effects on T cells that deserves further investigation.

Sign in / Sign up

Export Citation Format

Share Document