Activation of lymphocytes in vitro for immunotherapy of patients with melanoma

2021 ◽  
Vol 1 (31) ◽  
pp. 13-18
Author(s):  
E. V. Abakushina ◽  
Yu. V. Gel’m ◽  
E. Yu. Lyssuk
Keyword(s):  
T Lymphocyte ◽  
Adoptive Immunotherapy ◽  
Peripheral Blood ◽  
Activation Markers ◽  
Hla Dr ◽  
Activation Potential ◽  
Melanoma Patients ◽  
Positive Effect

This article describes a method for activating lymphocytes isolated from the peripheral blood of melanoma patients and cultured in a medium supplemented with IL‑2 and IL‑15. It was shown that in these terms, lymphocytes have an increased proliferative and activation potential. The combination of cytokines has a positive effect on cytotoxicity, viability and the expression of activation markers (CD38, CD69, CD25, HLA-DR and NKG2D) on NK- and T-lymphocyte, and may be recommended for the culture of lymphocytes in melanoma patients for the purpose of adoptive immunotherapy.

Long-Term Follow-up of Patients with Recurrent Malignant Gliomas Treated with Adjuvant Adoptive Immunotherapy

Neurosurgery ◽  
1991 ◽  
Vol 28 (1) ◽  
pp. 16-23 ◽  
Author(s):  
Kevin O. Lillehei ◽  
Dawn H. Mitchell ◽  
Stephen D. Johnson ◽  
Larry E. McCleary ◽  
Carol A. Kruse
Keyword(s):  
Survival Time ◽  
Adoptive Immunotherapy ◽  
Peripheral Blood ◽  
Interleukin 2 ◽  
Peripheral Blood Lymphocytes ◽  
Lak Cells ◽  
Prior Chemotherapy ◽  
Blood Lymphocytes ◽  
Significant Difference

Abstract Between August 1986 and October 1987, the Denver Brain Tumor Research Group conducted a clinical trial using autologous human recombinant interleukin-2 (rIL-2)-activated lymphocytes to treat 20 patients with recurrent high-grade gliomas. The trial involved surgical resection and/or decompression followed by intracavitary implantation of lymphokine-activated killer (LAK) cells and autologous stimulated lymphocytes (ASL) along with rIL-2 in a plasma clot. One month later, stimulated lymphocytes and rIL-2 were infused through a Rickham reservoir attached to a catheter directed into the tumor bed. The LAK cells were rIL-2-activated peripheral blood lymphocytes cultured for 4 days; the ASL were lectin- and rIL-2-activated peripheral blood lymphocytes cultured for 10 days. Of the 20 patients treated, 11 were evaluated as a group (mean age, 44 years, range, 15-61 years; mean Karnofsky rating, 69, range, 50-100; mean Decadron dose at entry, 14 mg/d. range, 0-32). The average number of lymphocytes implanted was 7.6 × 109 (range, 1.9-27.5 × 109), together with 1 to 4 × 106 U of rIL-2. To date, 10 of the 11 patients died, all from recurrent tumor growth. The median overall survival time was 63 weeks (range, 36-201; mean, 86). The median survival time after immunotherapy was 18 weeks (range, 11-151; mean, 39). No significant difference in survival after immunotherapy was found between those patients who had received previous chemotherapy and those who had not. The use of steroids or prior chemotherapy did not influence the in vitro generation of ASL or LAK cells. Prior chemotherapy did correlate, however, with diminished in vitro cytotoxicity against the natural killer-sensitive (K562) target cell by LAK cells (P < 0.05) but not that by ASL. There were no major adverse side effects. Although adoptive immunotherapy was safe and well tolerated, its therapeutic potential remains in question.

Vitamin D modulates the expression of HLA-DR and CD38 after in vitro activation of T-cells

2017 ◽  
Vol 29 (3) ◽  
Author(s):  
Simon Villegas-Ospina ◽  
Wbeimar Aguilar-Jimenez ◽  
Sandra M. Gonzalez ◽  
María T. Rugeles
Keyword(s):  
Vitamin D ◽  
Flow Cytometry ◽  
Healthy Subjects ◽  
Mononuclear Cells ◽  
Activation Markers ◽  
Hla Dr ◽  
In Vitro Activation ◽  
Cells Cultured

AbstractObjective:Vitamin D (VitD) is an anti-inflammatory hormone; however, some evidence shows that VitD may induce the expression of activation markers, such as CD38 and HLA-DR. We explored its effect on the expression of these markers on CD4Materials and methods:CD38 and HLA-DR expression was measured by flow cytometry in PHA/IL-2-activated mononuclear cells cultured under VitD precursors: three cholecalciferol (10Results:Cholecalciferol at 10Conclusion:Although no significant correlations were observed in vivo in healthy subjects, VitD treatment in vitro modulated immune activation by increasing the expression of CD38 and decreasing the proliferation of HLA-DR

scholarly journals Predicting therapeutic outcome in severe ulcerative colitis by measuring in vitro steroid sensitivity of proliferating peripheral blood lymphocytes

Gut ◽  
1999 ◽  
Vol 45 (3) ◽  
pp. 382-388 ◽  
Author(s):  
S D Hearing ◽  
M Norman ◽  
C S J Probert ◽  
N Haslam ◽  
C M Dayan
Keyword(s):  
Ulcerative Colitis ◽  
T Lymphocytes ◽  
Disease Severity ◽  
T Lymphocyte ◽  
Peripheral Blood ◽  
Steroid Treatment ◽  
Steroid Resistance ◽  
Severe Ulcerative Colitis ◽  
Steroid Sensitivity

BACKGROUNDUp to 29% of patients with severe ulcerative colitis (UC) fail to respond to steroid treatment and require surgery. Previous studies have failed to show a clear correlation between failure of steroid treatment in severe UC and measures of disease severity. The reasons for treatment failure therefore remain unknown.AIMTo investigate the hypothesis that patients with severe UC who fail to respond to steroid treatment have steroid resistant T lymphocytes.METHODSEighteen patients with severe UC were studied. After seven days’ treatment with high dose intravenous steroids they were classified as complete responders (CR), incomplete responders (IR), or treatment failures (TF). Within 48 hours of admission blood was taken and the antiproliferative effect of dexamethasone on phytohaemagglutinin stimulated peripheral blood T lymphocytes was measured. Maximum dexamethasone induced inhibition of proliferation (Imax) was measured.RESULTSIn vitro T lymphocyte steroid sensitivity of TF and IR patients was significantly less than that of CR patients. Both TF and 3/5 IR patients had an Imax of less than 60%; all CR patients had an Imax of greater than 60%. No significant correlation was seen between response to treatment and disease severity on admission. When in vitro T lymphocyte steroid sensitivity was remeasured three months later, there was no difference between the groups.CONCLUSIONSResults suggest that T lymphocyte steroid resistance is an important factor in determining response to steroid treatment in patients with severe UC and may be more predictive of outcome than disease severity.

scholarly journals Human bone marrow and peripheral blood T lymphocyte depletion: efficacy and effects of both T cells and monocytes on growth of hematopoietic progenitors

Blood ◽  
1985 ◽  
Vol 65 (3) ◽  
pp. 663-679
Author(s):  
L Levitt ◽  
TJ Kipps ◽  
EG Engleman ◽  
PL Greenberg
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocyte ◽  
Peripheral Blood ◽  
Cell Depletion ◽  
Target Cells ◽  
Facs Analysis ◽  
Hematopoietic Progenitors ◽  
T Cell Depletion

The efficacy of four separate methods of human bone marrow T lymphocyte depletion was assessed, and the effect of T cells and monocytes on in vitro growth of marrow (CFU-GEMM, BFU-E, and CFU-GM) and peripheral blood (BFU-E) hematopoietic progenitors was determined. Extent of T cell depletion was assessed by multiparameter fluorescent cell sorter (FACS) analysis and by functional studies. Cells staining positively by FACS analysis for one or more of three separate fluorescent pan-T cell monoclonal antibodies (MCAbs) comprised 8.4% to 9.5% of control marrow mononuclear cells (MNCs). T cells constituted 3.2% to 5.1% of marrow following single, sequential, or combination treatment with two different pan-T cell MCAbs (Leu 1 and TM1) plus complement, 1.5% to 2.2% of marrow following solid-phase immunoabsorption (“panning”), 0.2% of marrow after sheep cell rosetting, and only 0.05% of marrow after FACS selective cell sorting and gated separation. T cells made up 59% to 73% of control peripheral blood MNCs and 0.8% to 2.8% of peripheral MNCs following sheep cell rosetting plus treatment with Leu 1 MCAb and complement. Mitogen (PHA, Con A) and allogeneic MLC-induced blastogenic responses (stimulation indices, experimental/control or E/C) revealed a concordant decrement in marrow T cell function after MCAb plus complement (E/C of 3.9 to 9.0), after panning (E/C of 1.6 to 3.5) and after sheep cell rosetting (E/C of 0.7 to 1.3), compared with control marrow (E/C of 5.3 to 15.7). After T cell depletion, marrow BFU-E growth was 95% to 120% of control, CFU-GM growth was 90% to 108% of control, and CFU-GEMM growth was 89% to 111% of control. Marrow T cell and/or monocyte depletion did not alter erythropoietin-dependent BFU-E growth in the absence of Mo-conditioned medium (81% to 95% of control), and the addition of as many as 50 to 100 X 10(3) purified marrow monocytes or T cells to 10(5) autologous nonadherent T cell-depleted marrow target cells had a negligible (P greater than .1) effect on marrow BFU-E growth in vitro. Peripheral blood (PB) BFU-E/10(5) T- depleted target cells were 106% +/- 19% of expected; PB BFU-E growth was significantly diminished after monocyte depletion alone (7% +/- 6% of expected) or after monocyte plus T cell depletion (8% +/- 4% of expected).(ABSTRACT TRUNCATED AT 400 WORDS)

Abstract W P87: Characteristics of T-cells Infiltrating Ruptured Intracranial Aneurysm

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Roger M Krzyzewski ◽  
Magdalena K Stachura ◽  
Mariusz Krupa ◽  
Rafal Morga ◽  
Agnieszka Sagan ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Intracranial Aneurysm ◽  
Peripheral Blood ◽  
Histological Finding ◽  
Cell Phenotype ◽  
Double Negative ◽  
Activation Markers ◽  
Hla Dr ◽  
Ruptured Intracranial Aneurysm

Introduction: Recently the role of adaptive immunity has been implied by microarray studies. But the results are contradictory. T-cell infiltration is a frequent histological finding in ruptured IA, T-cell phenotype, characteristic and true quantitation remains unknown. We preformed a prospective study to determine the subpopulation and expression of activation markers of T-cells infiltrating ruptured IA in relation to peripheral blood. Hypothesis: IA have different subsets and activation levels of T-cells than peripheral blood. Methods: We collected the tissue of ruptured IA of 8 patients operated on within 24 hours after subarachnoid hemorrhage symptoms onset. IA tissue was digested, stained with fluorescently labeled monoclonal antibodies and submitted to flow cytometry. In addition we collected and analyzed venous blood from 6 age, sex and risk factor-matched controls. Results: CD4+ cells are less prevalent in IA tissue than in peripheral blood (42.14±17.28 vs. 65.88±5.32%; p=0.011), while there was no difference in CD8+ T-cells infiltrating IA (30.28±9.07 vs. 27.78±5.45%; p=0.585), and double negative (CD4-CD8-CD3+) T-cells were more prevalent in wall of IA than in circulation, (15.68±11.94 vs. 2.81±1.32%; p=0.026). Importantly, CD4+ infiltrating IA wall showed higher expression of HLA-DR (25.9±6.42 vs. 9.19± 3.58%; p<0.001) higher expression of CD 69 (26.8±19.66 vs. 2.73±0.93%; p=0.014). Similarly, there significantly more CD8+ cells showed HLA-DR+ in the IA than in blood. (45.96±15.57 vs. 22.47±11.46%; p=0.018) and CD69 (30.32±22.73 vs. 5.03±1.55%; p=0.022). Double negative cells in IA also had higher expression of HLA-DR (46.56±21.40 vs. 22.58±5.1%; p=0.025), CD69 (31.05±16.79 vs. 7.83±2.05%; p=0.016). Conclusion: The tissue of ruptured IA is highly infiltrated by T-cells which show high expression of activation markers such as CD69 or HLA-DR. The importance of these cells to immunopathogenesis of intracranial aneurysm rupture should be further characterized.

scholarly journals Immunostimulants in respiratory diseases: focus on Pidotimod

2019 ◽  
Vol 14 ◽  
Author(s):  
Francesca Puggioni ◽  
Magna Alves-Correia ◽  
Manar-Farouk Mohamed ◽  
Niccolò Stomeo ◽  
Riccardo Mager ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Respiratory Diseases ◽  
Dendritic Cell Maturation ◽  
Immunomodulatory Activity ◽  
T Lymphocyte Subsets ◽  
T Lymphocyte Proliferation ◽  
Hla Dr ◽  
Airway Infections ◽  
Tract Infections

Usefulness of Pidotimod and its role as immunostimulant, has been discussed, we know, for several decades. Nevertheless, there is still much to know. Understanding its mechanisms and its potential usefulness in airway infections and its prevention, asthma both Th2 and non Th2 type, bronchiectasis, as adjuvant in vaccination and in allergen immunotherapy still remains to clearly unveil. The aim of this paper was to provide a useful updated review of the role of the main available immunostimulants, giving particular focus on Pidotimod use and its potentials utility in respiratory diseases. Pidotimod showed its usefulness in reducing need for antibiotics in airway infections, increasing the level of immunoglobulins (IgA, IgM, IgG) and T-lymphocyte subsets (CD3+, CD4+) endowed with immunomodulatory activity that affect both innate and adaptive immune responses. Higher expression of TLR2 and of HLA-DR molecules, induction of dendritic cell maturation and release of pro-inflammatory molecules, stimulation of T lymphocyte proliferation and differentiation toward a Th1 phenotype, as well as an increase of the phagocytosis have been demonstrated to be associated with Pidotimod in in vitro studies. All these activities are potentially useful for several respiratory conditions such as asthma, COPD, and recurrent respiratory tract infections.

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