Peculiarities of the immune status of patients with multidrug­resistant pulmonary tuberculosis after application of treatment regimens with bedaquiline and linezolid

2021 ◽  
pp. 30-35
Author(s):  
N.Ye. Lapovets ◽  
O.A. Tkach ◽  
I.L. Platonova ◽  
L.Ye. Lapovets ◽  
V.M. Akimova
Keyword(s):  
Immune System ◽  
T Cell ◽  
T Lymphocytes ◽  
Pulmonary Tuberculosis ◽  
Differential Count ◽  
Hypersensitivity Reactions ◽  
Treatment Regimens ◽  
Fourth Type ◽  
T Cell Immunodeficiency ◽  
T Helpers

Objective — to investigate immuno-metabolic homeostasis in patients with new and recurrent cases of destructive forms of multidrug-resistant pulmonary tuberculosis (MDR-PTB) after treatment with bedaquiline and linezolid. Materials and methods. A clinical and laboratory examination of 175 people with MDR-PTB (89 patients with new cases and 86 patients with recurrent cases of destructive forms of MDR-PTB). The study was performed before and after treatment with bedaquiline and linezolid. The total leukocytes count (L), the leukocyte differential count (leukocyte formula), was determined in all subjects, The content of populations and subpopulations of lymphocytes were calculated using monoclonal antibodies to CD3+, CD4+, CD8+, CD19+, CD23+, CD56+ lymphocytes antigen in the reaction of indirect immunofluorescence. Quantitative determination of serum immunoglobulins was performed by Manchini radial immunodif­fusion in a gel. The level of circulating immune complexes (CIC) was determined by the spectrophoto­metric method by precipitation in polyethylene glycol. Results and discussion. In patients with new cases of destructive forms of MDR-PTB to treatment revealed hypersensitivity reactions of the first and the fourth type. Expressed activation of humoral and killer parts of immunity detected. In patients with recurrent cases of destructive forms of MDR-PTB before treatment, there are pronounced hypersensitivity reactions of the fourth type and activation of the humoral and killer parts of the immune system.Patients with new cases of destructive forms of MDR-PTB after application of treatment regimens with bedaquiline and linezolid have hypersensitivity reactions of the first and fourth types. Activation of humo­ral and killer parts of immunity detected. In patients with recurrent cases of destructive forms of MDR-PTB after the application of treatment regimens with bedaquiline and linezolid revealed a pronounced hypersensitivity reaction of the first type and activation of the killer and humoral parts of the immune system. Conclusions. In patients with new cases of destructive forms of MDR-PTB before treatment revealed T-cell immunodeficiency, which is expressed by a decrease in the level of T-lymphocytes (1.7 times relative to normal) and T-helpers (twice below normal). In patients with recurrent cases of destructive forms of MDR-PTB before treatment revealed T-cell immunodeficiency with a marked decrease in the level of T-lymphocytes (1.8 times normal) and T-helpers (1.8 times below normal). In patients with new cases of destructive forms of MDR-PTB after the application of treatment regimens with bedaquiline and linezolid revealed activation of the T-cell immune system due to increased levels of T-suppressors. In patients with recurrent cases of destructive forms of MDR-PTB after the application of treatment regimens with bedaquiline and linezolid revealed T-cell immunodeficiency due to the reduced content of T-lymphocytes (1.5 times below normal), namely T-helpers (1.9 times lower than normal).

Lenalidomide IS Able to Restore Immune SYSTEM IN MULTIPLE MYELOMA PATIENTS.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4909-4909 ◽  
Author(s):  
Annalisa Chiarenza ◽  
Nunziatina Parrinello ◽  
Piera La Cava ◽  
Eleonora Spina ◽  
Daniele Tibullo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Immune System ◽  
T Cell ◽  
T Lymphocytes ◽  
Mononuclear Cells ◽  
Conflicts Of Interest ◽  
Gradient Centrifugation ◽  
Target Cells ◽  
First Line ◽  
Number Of Patients

Abstract Abstract 4909 LENALIDOMIDE IS ABLE TO RESTORE IMMUNE SYSTEM IN MULTIPLE MYELOMA PATIENTS Annalisa Chiarenza, Nunziatina Parrinello, Piera La Cava, Eleonora Spina, Daniele Tibullo, Cesarina Giallongo, Maide Cavalli, Alessandra Romano, Paolo Fiumara, Giuseppe A. Palumbo, Francesco Di Raimondo Background Multiple myeloma (MM) is a malignant plasma-cell proliferative disorder associated with dysfunctional T-cell responses. The immunomodulatory Thal derivative (IMiD) CC-5013 (lenalidomide) appears to be a promising agent for the treatment of myeloma. Although the exact antitumor mechanism of action of lenalidomide is unknown, a number of mechanisms are postulated to be responsible for it's activity (inhibition of angiogenesis, direct antiproliferative and proapoptotic effects on MM cells, suppression of pro-inflammatory cytokines, modulation of myeloma-stromal cells adhesive interactions). In addition, it has been demonstrated that lenalidomide in vitro is able to enhance T cell proliferation and to promotes ADCC. In this study we evaluated if MM patients have a deficit of T-reg (CD4+, CD25+, and FOXP3+) and of T lymphocytes bearing CD200 (a tolerogenic molecule) and the effect of lenalidomide treatment on these parameters. In addition, we investigated whether lenalidomide could improve ex vivo the ADCC against myeloma cells. Materials and methods Eight patients with previously untreated MM (median age 56 years) were treated with lenalidomide plus dexamethasone as first line therapy. Lenalidomide was given orally 25 mg daily on days 1 to 21 of a 28-day cycle. Dexamethasone was given orally 40 mg daily on days 1, 8, 15, 22 of each cycle. All patients were evaluable for response and toxicity. Peripheral blood mononuclear cells (PBMNc) were obtained from MM patients using density gradient centrifugation (Fycoll) under sterile condictions, at the beginning of treatment and after 4 cycles of therapy. The percentage of T-reg (CD4+CD25+FOXP3+) and the expression of CD200 on T- lymphocytes were evaluated by cytometry. Twelve healthy subjects were used as control. Moreover, PBMNc (effector cells, E) were incubated with MM cells line ARH-77 (target cells, T), previously labelled with CFDA,SE (carboxyfluorescein diacetate, succinimidyl ester) as a tracing fluorescent marker, in culture medium (RPMI-1640, 10%FCS, 1%penicillin/streptomycin) at different concentration (T/E ratio 1:20, 1:40). After 18-24 h co-colture cells were analyzed by flow cytometry and MM plasma cells cytotoxicity was calculated as the percentage of positive CFDA,SE/propidium cells. Myeloma cell viability was determined by tripan blue esclusion and apoptosis was also evaluated using Annexin V/propidium assay. Two MM patients treated in first line with a combination of Velcade, Thalidomide and Dexamethasone (VTD) were used as control and the experiments were performed in duplicate. Results MM patients have a significantly lower rate of CD4+/CD25+/FOXP3+ and CD200+/CD3+ than normal (28,3±14,9/mmc and 37,8±24,7 /mmc vs 79,3±27,8 and 79,5± 48,9)(p=0,0001 and p=0,01 respectively). In our study, lenalidomide treatment resulted in an increase both of Treg cells and T-lymphocytes espressing CD200. This improvement is not statistically significant probably due to the low number of patients examined (tab I). More important, we observed that PBMC derived from patients treated with lenalidomide showed an increase ability to kill a target MM cell line compared to PBMC collected at diagnosis (CFDA,SE/propidium cells 11% vs 68%). This effect was more prominent in patients treated with lenalidomide than in MM patients treated with VTD (CFDA,SE/propidium cells 12% vs 39%), Fig.1. Conclusions Our data emphasize the role of lenalidomide in modulating the endogenous tumor-specific immune response and underline the anti-myeloma activity of these new class of drugs. Disclosures No relevant conflicts of interest to declare.

scholarly journals Assessment of CLA+T-cell subpopulations in the blood of patients with chronic dermatoses

2020 ◽  
Vol 96 (4) ◽  
pp. 22-31
Author(s):  
Alexander V. Patrushev ◽  
Alexey V. Samtsov ◽  
Vladimir Yu. Nikitin ◽  
Alexey V. Soukharev ◽  
Oksana P. Gumilevskaya ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
T Cell ◽  
T Lymphocytes ◽  
Lichen Planus ◽  
Cytotoxic T Lymphocytes ◽  
Relative Number ◽  
Cell Subpopulations ◽  
T Cell Subpopulations ◽  
The Relationship ◽  
T Helpers

Background. CLA+T-cell are an important component of skin-associated lymphoid tissue, and thus determine the pathogenesis of many immuno-mediated dermatoses. Aims. Determine the relative number of CLA+T-cell subpopulations in the peripheral blood of patients with psoriasis, lichen planus and atopic dermatitis, as well as assess their impact on the severity of dermatoses. Materials and methods. We examined 82 patients with psoriasis aged 19 to 62 years, 54 patients with lichen planus (LP) aged 18 to 54 years, 44 patients with atopic dermatitis (AD) aged 18 to 44 years, as well as 20 practically healthy individuals aged 18 to 52 years who were admitted to the clinic for the removal of benign skin neoplasms. All patients underwent a standard clinical examination with the determination of indicators that characterize the severity of dermatosis: PASI (Psoriasis Area and Severity Index) for patients with psoriasis, IPSLP (index of prevalence and severity of lichen planus) for patients with lichen planus and SCORAD (Scoring of Atopic Dermatitis) for patients with atopic dermatitis. Defining subpopulations CLA+T-lymphocytes were carried out on a flow cytometer Cytomics FC500 by Beckman Coulter using appropriate combinations of direct monoclonal antibodies and isotopic controls. The groups were compared using the nonparametric Mann Whitney test, and the differences were considered significant at p0,05. To analyze the relationship between the severity of dermatosis and the relative content of subpopulations CLA+T-cells used Spearman's rank correlation coefficient. Results. In patients with psoriasis, a significant increase in the percentage of the total number of T-lymphocytes positive for CLA (CLA+CD3+) and T-helpers positive for CLA (CLA+CD4+) (p=0,002 and 8,5104, respectively), in patients with PL and AD only CLA+CD4+ lymphocytes (p=0,028 and 0,003, respectively). In the progressive period of psoriasis, a direct moderate correlation was found between the circulating subpopulation of cytotoxic T lymphocytes positive for CLA (CLA+CD8+) and the PASI index (rs=0,47; p0,001), in the acute period of AD between the CLA+CD3+ subpopulations and CLA+CD4+ cells and the SCORAD index (rs=0,53; p 0,001 and rs=0,57; p0,001, respectively). In PL, the severity of the course of dermatosis was not accompanied by any significant changes in the CLA-positive T-cell subpopulations. Conclusion. The results of the study confirmed the important role of CLA+T cell subpopulations in the development of chronic dermatoses. In all groups (psoriasis, LP and AD), an increase in the relative number of CLA+CD4+ T-helpers was noted compared with the control group. The relationship between the severity of psoriasis and the relative number of CLA+CD8+ cytotoxic T-lymphocytes, and the severity of AD with CLA+CD3+ and CLA+CD4+ T-helpers is also shown.

scholarly journals Different Cytokine Production and Effector/Memory Dynamics of αβ+ or γδ+ T-Cell Subsets in the Peripheral Blood of Patients with Active Pulmonary Tuberculosis

2003 ◽  
Vol 16 (3) ◽  
pp. 247-252 ◽  
Author(s):  
C. Gioia ◽  
C. Agrati ◽  
D. Goletti ◽  
D. Vincenti ◽  
S. Carrara ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Pulmonary Tuberculosis ◽  
Peripheral Blood ◽  
Cell Subset ◽  
T Cell Response ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Cell Dynamics ◽  
Active Pulmonary Tuberculosis

Immunity to M.tuberculosis (MTB) infection consists of interactions between various T-cell subsets that control the infection and prevent further reactivation. We analysed the effector/memory T-cell dynamics and cytokines production in the peripheral blood of patients with pulmonary tuberculosis (TB). We observed that the frequency of CD4+ T-cell effectors was significantly increased during active TB, confirming a major role of this T-cell subset in TB immunity. Pre-terminally differentiated CD8+ T-lymphocytes were increased in the peripheral blood as well. In contrast, we observed a reduced number of effector mycobacteria-reactive γδ+ T-lymphocytes with a specific defects in reacting to mycobacterial nonpeptidic antigens, suggesting that this innate response is rapidly lost during TB infection. Nevertheless, the frequency of γδ+ T-cells effectors in TB patients was higher than the αβ+ T-cell response to peptide from MTB-ESAT-6 protein and quantitatively similar to PPD reactivity. Thus, αβ+and γδ+ T-cell differentiation and function are differently triggered by active TB infection.

scholarly journals ROLE OF DISTINCT CD4+ T-CELL SUBSETS IN HIV-INFECTION PATHOGENESIS

2020 ◽  
pp. 236-246
Author(s):  
E. V. Saidakova ◽  
Keyword(s):  
Immune System ◽  
T Cell ◽  
T Lymphocytes ◽  
Hiv Infection ◽  
T Lymphocyte ◽  
Highly Active Antiretroviral Therapy ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Effector Memory ◽  
T Lymphocyte Subsets

CD4+ T-cell pool is composed of cells residing in different maturation stages. Naive CD4+ T-lymphocytes, CD4+ stem memory T-cells, CD4+ central and effector memory T-lymphocytes perform var-ious functions in maintaining the immune system homeostasis. Despite phenotypic differences, each of those cells can be infected with HIV. Specific features of distinct CD4+ T-lymphocyte subsets determine their role in HIV-infection pathogenesis. By analyzing changes of CD4+ T-lymphocyte subset composi-tion, one can estimate the degree of the immune system damage and make predictions of immune recov-ery under highly active antiretroviral therapy. The article summarizes the main events occurring with CD4+ T-cell subsets during HIV-infection.

scholarly journals Discordance of Twin Placentas for Multifocal Eosinophilic/T-cell Chorionic Vasculitis

2018 ◽  
Vol 22 (1) ◽  
pp. 40-44
Author(s):  
Erik W Nohr ◽  
James R Wright
Keyword(s):  
Immune System ◽  
T Cell ◽  
T Lymphocytes ◽  
Monozygotic Twin ◽  
Vascular Territory ◽  
Twin Pregnancies ◽  
Fetal Immune System

Eosinophilic/T-cell chorionic vasculitis (ETCV) is an idiopathic placental lesion characterized by chorionic vasculitis composed predominantly of eosinophils and CD3+ T lymphocytes. It usually presents as a unifocal lesion, but a subset have multifocal involvement. We report 4 Di-Di and 2 Di-Mo twins sharing fused placental discs with discordant circulatory involvement by multifocal ETCV. The findings are difficult to explain by sampling alone. The limitation of ETCV to 1 fetus’s vascular territory in monozygotic twin pregnancies is difficult to explain but could provide insights into the fetal immune system and the etiology of ETCV.

Prolactin receptor expression in lymphocytes from patients with hyperprolactinemia or acromegaly

1995 ◽  
Vol 147 (2) ◽  
pp. 353-359 ◽  
Author(s):  
M C Leite-de-Moraes ◽  
P Touraine ◽  
P A Kelly ◽  
F Kuttenn ◽  
M Dardenne
Keyword(s):  
Immune System ◽  
T Cell ◽  
T Lymphocytes ◽  
B Lymphocytes ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Matched Control ◽  
Prolactin Receptor ◽  
Receptor Expression ◽  
Prolactin Receptors

Abstract Previous reports demonstrated that prolactin receptors (PRL-R) are widely expressed on cells of the immune system. We analyzed a possible regulation of PRL-R expression on human mononucleated blood cells by prolactin (PRL) itself. PRL-R expression was analyzed by immunofluorescence on T and B lymphocytes and monocytes from peripheral blood mononucleated cells (PBMC) of patients with hyperprolactinemia or acromegaly compared with sex- and age-matched control subjects. The frequency of PRL-R positive cells and the intensity of PRL-R expression was only modified among the CD8+ T cell population of hyperprolactinemic patients with macroadenoma. No correlation was reported between PRL-R expression and circulating PRL levels. The percentage of PRL-R+ cells on B or T lymphocytes and monocytes as well as the capacity of PBMC to proliferate in response to T cell mitogens were not significantly different in bromocriptine-treated compared with untreated patients. These findings suggest that factors other than pituitary PRL play the major role in regulating PRL-R expression on cells of the immune system. Journal of Endocrinology (1995) 147, 353–359

scholarly journals Changes in the immune status of patients with metastatic solid tumors during stereotactic radiation therapy: dependence on dose and amount of irradiated metastasis

2021 ◽  
Vol 67 (3) ◽  
pp. 391-396
Author(s):  
Anton Zozulia ◽  
Irina Baldueva ◽  
Sergei Novikov ◽  
Dmitrii Girdiuk ◽  
Natalia Emelianova ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
T Cell ◽  
T Lymphocytes ◽  
Solid Tumors ◽  
Malignant Tumors ◽  
Cell Immune Response ◽  
Immunological Parameters ◽  
Hla Dr ◽  
T Helpers ◽  
Higher Doses

Purpose. To evaluate immunological status in patients with metastatic forms of solid tumors before and at different intervals after stereotactic body radiation therapy (SBRT) of metastatic lesions depending on the dose and the number of irradiated metastasis. Materials and methods. A quantitative assessment and analysis of blood immunological parameters was conducted before irradiation, via 3-4 weeks and via 6-8 weeks after SBRT in patients with malignant tumors with oligometastases in the liver and lungs, in groups with a total focal dose (TFD ≤ 45 Gy ) and TFD> 45 Gy, and also in groups with irradiation of one metastases and two or more. All peripheral blood samples were analyzed by flow cytometry. Statistical analysis was performed using Friedman and Nemenyi criteria. Results. 3-4 weeks after the end of SBRT, when using higher doses (TFD> 45 Gy), we observed statistically significant increase of T-lymphocytes (CD3+CD19-); T-helpers (CD3+CD4+); activated T-helpers (CD3+CD4+HLA-DR+); activated cytotoxic T-lymphocytes (CD3+СD8+HLA-DR+). Decreasing of B-lymphocytes (CD3+CD19-) was observed in both dose groups (TFD ≤ 45 Gy and TFD > 45 Gy). We also noted the activation of the T-cell link of immunity both in the group with irradiation of one metastatic lesion, and in the group where 2 or more metastases were exposed to irradiation. Conclusion. Using of higher doses of SBRT is associated with a more activated antitumor T-cell immune response, while the analysis of groups of patients with different ammount of irradiated metastasis currently requires further research.

scholarly journals Productive Infection of Neonatal CD8+ T Lymphocytes by HIV-1

1998 ◽  
Vol 187 (7) ◽  
pp. 1139-1144 ◽  
Author(s):  
Liang Peng Yang ◽  
James L. Riley ◽  
Richard G. Carroll ◽  
Carl H. June ◽  
James Hoxie ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
T Lymphocytes ◽  
Hiv Infection ◽  
Cd8 T Cells ◽  
Productive Infection ◽  
Target Cells ◽  
Cd8 T Lymphocytes ◽  
Hiv 1

CD8+ T lymphocytes confer significant but ultimately insufficient protection against HIV infection. Here we report that activated neonatal CD8+ T cells can be productively infected in vitro by macrophage-tropic (M-tropic) HIV-1 isolates, which are responsible for disease transmission, whereas they are resistant to T cell–tropic (T-tropic) HIV strains. Physiological activation of CD8-α/β+ CD4− T cell receptor–α/β+ neonatal T cells, including activation by allogeneic dendritic cells, induces the accumulation of CD4 messenger RNA and the expression of CD4 Ag on the cell surface. The large majority of anti-CD3/B7.1–activated cord blood CD8+ T cells coexpress CD4, the primary HIV receptor, as well as CCR5 and CXCR4, the coreceptors used by M- and T-tropic HIV-1 strains, respectively, to enter target cells. These findings are relevant to the rapid progression of neonatal HIV infection. Infection of primary HIV-specific CD8+ T cells may compromise their survival and thus significantly contribute to the failure of the immune system to control the infection. Furthermore, these results indicate a previously unsuspected level of plasticity in the neonatal immune system in the regulation of CD4 expression by costimulation.

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