Features of T lymphocyte subpopulation profile in patients with ankylosing spondylitis undergoing genetically engineered biological therapy

The aim of current study was to compare profiles of T cell subsets in the patients with ankylosing spondylitis (AS) who received different modes of genetically engineered biological therapy (GEBT). The research involved 58 patients aged 20 to 58 years diagnosed with AS and treated with anti-TNFα and antiIL-17 drugs, as well as those receiving common anti-inflammatory therapy. The AS diagnostics was based on the modified New York criteria. Disease activity was assessed by means of nomenclature approved by the Assessment of Spondyloarthritis International Society and Outcome Measures in Rheumatology. 45 healthy people aged 18 to 57 were included into the control group. Peripheral blood T cell subsets were analysed by multicolor flow cytometry. It was found that the T lymphocyte subpopulation profiles in AS patients showed significant differences depending on the therapy type. First, T lymphocyte counts were decreased in AS patients receiving traditional anti-inflammatory therapy, whereas relative numbers of T cells with high levels of effector potential and cytokine secretion were increased. Negative correlations between the levels of effector memory and pre-effector cytotoxic T cells and other laboratory and clinical indexes of inflammatory activity in AS may reflect lower efficiency of traditional therapy. Next, the levels of main T cell subsets in AS patients during antiIL-17 therapy fully corresponded to the control values. However, based on numerous correlations between immunological and clinical laboratory parameters, it was concluded that anti-IL-17 therapy had an inhibitory effect on the joint inflammation activity, while the state of T cell subsets was mainly dependent on standard anti-inflammatory therapy. The most pronounced changes in T cell subsets were found in AS patients during anti-TNFα therapy was associated with decreased effector potential of Th cells and cytotoxic T lymphocytes. At the same time, the lowest frequency of extraskeletal manifestations was found in AS patients treated with anti-TNFα drugs. Finally, the higher efficiency of GEBT, compared with conventional methods of therapy, is determined by the effects upon immune targets of AS pathogenesis which manifested, e.g., by changes in the T lymphocyte subpopulation profile. Moreover, usage of anti-TNFα versus anti-IL-17 inhibitors was associated with greater effect upon phenotypic profile of T cells.

Efficiency of human plague vaccination in tuvinian natural plague focus. Message 2: dynamics of immune status indicators after revaccination

Relevance. In Russia, the live plague vaccine (LPV) is used for specific prophylaxis of plague. Immunological monitoring of humans vaccinated by LPV in order to search for informative diagnostic markers, as well as to improve the tactics of epidemiological surveillance of plague enzootic territories is an urgent area of research.The aim is to assess the parameters of cellular and humoral immunity in humans revaccinated by LPV who permanently reside on territory of the Tuvinian natural plague focus.Materials and methods. The study involved 76 volunteers from the Republic of Tuva, revaccinated by LPV. Blood sampling was performed before vaccination and 1, 3, and 6 months after revaccination. The study included the determination of cytokine production (IFN-γ, IL-4, TNF-α), specific antibodies, immunoglobulins (IgM, IgG, IgA and IgE) and lymphocyte subpopulation composition (CD3, CD4, CD8, CD16, CD19, immunoregulatory index).Results. A decrease in IgG and IgM and an increase in IgA were found after vaccination with LPV and their increase after revaccination. Correlation relationships were revealed between immunoglobulins, B cells and IL-4. Revaccination leads to an increase seroconversion. The activation of humoral immunity in humans vaccinated against plague is also evidenced by dynamics of changes in the subpopulation composition: an increase in B-lymphocytes and natural killer cells, a decrease in T-helpers and immunoregulatory index, and cellular immunity stimulation is an increase in spontaneous and induced production of pro- and anti-inflammatory cytokines.Conclusion. It has been shown that LPV is capable of causing the body’s immune restructuring and activating the cellular and humoral mechanisms of immunological protection. For a complete understanding of the development and preservation of antiplague immunity, it is necessary to continue the annual immunological monitoring of the population living on the territory of the Tuvinian natural plague focus, using additional modern research methods.

Effect of vitiligo treatment by compound Glycyrrhizin combined with fractional laser and Triamcinolone Acetonide injection on T Lymphocyte subpopulation

Objectives: To discuss the effective mechanism of vitiligo treatment by compound glycyrrhizin combined with fractional laser and triamcinolone acetonide injection. Methods: Forty-two patients with vitiligo vulgaris in the stable phase were classified into combined group (19 cases) and medicine group (23) admitted in dermatology department, Baoding First Central Hospital from January 2017 to July 2018. Both groups took 50mg compound glycyrrhizin orally three times per day, and applied halometasone cream externally once per day. Based on this treatment method, after the combined group adopted fractional laser, triamcinolone acetonide injection encapsulation was used immediately. After the treatment for six months, the curative effect was judged for both groups. Flow cytometry was used to test the changes of T lymphocyte subpopulation in peripheral blood before and after treatment. Meanwhile, immunohistochemical method was adopted to determine CD4+ and CD8+ T lymphocyte expression level. Besides, the normal control group was set up. Results: The efficacy of combined group and medicine group were 73.68% and 56.52% respectively, P<0.05. The comparison of CD3+, CD4+, CD8+ and CD4+/CD8+ T lymphocyte level in serum and skin damage before and after treatment had no statistical significance (P>0.05). Serum CD4+ T cells of vitiligo patients reduced, compared with the normal control group (P<0.05), and CD4+/CD8+ declined (P<0.05). CD4+ and CD8+ T lymphocytes at the skin damage of patients increased, compared with normal control group (P<0.05). Conclusions: Compound glycyrrhizin combined with fractional laser and triamcinolone acetonide injection has good clinical effect in the treatment of vitiligo vulgaris in the stable phase, and its effective mechanism may have nothing to do with T lymphocyte subpopulation. doi: https://doi.org/10.12669/pjms.38.1.4412 How to cite this:Li L, Gao L, Zhao Y. Effect of vitiligo treatment by compound Glycyrrhizin combined with fractional laser and Triamcinolone Acetonide injection on T Lymphocyte subpopulation. Pak J Med Sci. 2022;38(1):---------. doi: https://doi.org/10.12669/pjms.38.1.4412 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Ganoderma formosanum Exopolysaccharides Inhibit Tumor Growth via Immunomodulation

Ganoderma formosanum (GF) is a medicinal mushroom endemic to Taiwan. Previous research established the optimal culture conditions to produce exopolysaccharide rich in β-glucan (GF-EPS) from submerged fermentation of GF. The present study investigated the antitumor effects of GF-EPS in a Lewis lung carcinoma cell (LLC1) tumor-bearing mice model. In the preventive model, GF-EPS was orally administered to mice before LLC1 injection. In the therapeutic model, GF-EPS oral administration was initiated five days after tumor cell injection. The tumor size and body weight of the mice were recorded. After sacrifice, the lymphocyte subpopulation was analyzed using flow cytometry. Spleen tissues were used to analyze cytokine mRNA expression. The results showed that GF-EPS (80 mg/kg) effectively suppressed LLC1 tumor growth in both the preventive and therapeutic models. GF-EPS administration increased the proportion of natural killer cells in the spleen and activated gene expression of several cytokines. Our results provide evidence that GF-EPS promotes tumor inhibition through immunomodulation in tumor-bearing mice.

CO-EXPRESSION OF MEMBRANE-BOUND TUMOR NECROSIS FACTOR-α RECEPTORS IN MAJOR SUBPOPULATIONS OF IMMUNOCOMPETENT CELLS IN HEALTHY INDIVIDUALS AND PATIENTS WITH RHEUMATOID ARTHRITIS AS WELL AS BRONCHIAL ASTHMA

A pleiotropic cytokine TNFα is an important inflammatory mediator of a number of diseases; its biological functions are fulfilled through two different receptors, TNFR1 and TNFR2. Changes in the ratio between these types of receptors shifting the balance between the pro-apoptotic and proliferation signaling pathways play a crucial role in eliciting the cell response to TNFα. The pathological processes in the body can alter the levels of TNFR1 and TNFR2 expression on the cells involved in disease development. Therefore, this study was aimed at investigating the level of co-expression of type 1 and 2 TNFα receptors in the major subpopulations of peripheral blood cells in patients with rheumatoid arthritis (RA) and bronchial asthma (BA). The greatest changes in the percentage of cells expressing TNFR1 and TNFR2 were revealed for the B-lymphocyte subpopulation. For the T-lymphocyte subpopulation, there were some differences in the percentage of cells expressing exclusively TNFR1 in RA and BA patients compared with those in healthy subjects, as well as between the RA and BA groups. A higher percentage of double-negative monocytes was observed in patients with BA and RA compared to healthy subjects. These findings indicate that the coexpression profile of TNFR1 and TNFR2 receptors in patients with RA and BA differ within these groups as well as compared to that in healthy subjects. These immune cell populations are actively involved in the pathogenesis of both rheumatoid arthritis and bronchial asthma, so the results may indicate that these cells might show different responses to TNFα as the percentage and the number of receptors on their surface vary.

Clinical Efficacy and Safety of Shashen Maidong Decoction in the Treatment of Pediatric Mycoplasma Pneumonia: A Systematic Review and Meta-Analysis

Objective: This study was intended to provide data to support the effect of Shashen Maidong Decoction in improving mycoplasma pneumonia in pediatric patients through systematic evaluation.Methods: PubMed, the Web of Science, EMbase, CNKI, CQVIP, Wan-Fang, and CBM databases were comprehensively searched from established in June 2021. Randomized controlled trials of TRQI were selected by screening the literature and extracting information. The Cochrane RCT Evaluation Manual was used to evaluate the methodological quality of all included studies, and Meta-analysis was performed using Stata 14.0 and Review Manager 5.4 software.Results: A total of 1,127 patients from 12 clinical studies met the inclusion criteria. Meta-analysis results showed that the treatment group of Shashen Maidong Decoction was able to significantly increase the overall efficiency level and significantly reduce the incidence of adverse reactions, time for disappearance of cough, time for relief of cough, time for defervescence, time for disappearance of lung rales, time for return to normal of chest X-ray, T lymphocyte subpopulation (CD3+) and tumor necrosis factor-α (TNF-α) and other index levels (p &lt; 0.05).Conclusion: Shashen Maidong Decoction has a significant improvement in the levels of relevant indexes in pediatric mycoplasma pneumonia, which provides a basis for the safety and efficacy of pediatric mycoplasma pneumonia. However, due to the small sample size included in the study, the study quality was not high, and more randomized controlled trials of high quality are required for further validation.

γδ T Cells for Leukemia Immunotherapy: New and Expanding Trends

Recently, many discoveries have elucidated the cellular and molecular diversity in the leukemic microenvironment and improved our knowledge regarding their complex nature. This has allowed the development of new therapeutic strategies against leukemia. Advances in biotechnology and the current understanding of T cell-engineering have led to new approaches in this fight, thus improving cell-mediated immune response against cancer. However, most of the investigations focus only on conventional cytotoxic cells, while ignoring the potential of unconventional T cells that until now have been little studied. γδ T cells are a unique lymphocyte subpopulation that has an extensive repertoire of tumor sensing and may have new immunotherapeutic applications in a wide range of tumors. The ability to respond regardless of human leukocyte antigen (HLA) expression, the secretion of antitumor mediators and high functional plasticity are hallmarks of γδ T cells, and are ones that make them a promising alternative in the field of cell therapy. Despite this situation, in particular cases, the leukemic microenvironment can adopt strategies to circumvent the antitumor response of these lymphocytes, causing their exhaustion or polarization to a tumor-promoting phenotype. Intervening in this crosstalk can improve their capabilities and clinical applications and can make them key components in new therapeutic antileukemic approaches. In this review, we highlight several characteristics of γδ T cells and their interactions in leukemia. Furthermore, we explore strategies for maximizing their antitumor functions, aiming to illustrate the findings destined for a better mobilization of γδ T cells against the tumor. Finally, we outline our perspectives on their therapeutic applicability and indicate outstanding issues for future basic and clinical leukemia research, in the hope of contributing to the advancement of studies on γδ T cells in cancer immunotherapy.