Expression of CD226 on γδ T cells is lower in advanced chronic lymphocytic leukemia and correlates with IgA, IgG and LDH levels.

BACKGROUND: Gamma-delta (γδ) T cells comprise an important subset of human T cells, responding to viral and bacterial infections, and are significant for cancer immunosurveillance. Human γδ T cells are divided into 5 major subsets, namely Vδ1-Vδ5, of which the latter 3 have limited available literature. At present, Vδ2 is the most studied subpopulation. OBJECTIVES: In the current paper, we focused on non-Vδ2 cells in chronic lymphocytic leukemia (CLL). We assessed the expression of co-inhibitory checkpoint receptors (CTLA-4, PD-1 and TIGIT) and co-stimulatory (CD226 and NKp30) molecules separately on Vδ1 and Vδ3-Vδ5 cells. MATERIAL AND METHODS: We assessed γδ T cells for their expression of both cytotoxicity-related (NKp30, CD226) and co-inhibitory (PD-1, TIGIT) molecules with flow cytometry in CLL patients. Moreover, we evaluated the expression of TIGIT and CD226 ligand (PVR , CD155) in neoplastic B cells in CLL patients with quantitative real-time polymerase chain reaction (qPCR). RESULTS: A significant accumulation of Vδ1 T cells was noted, while no difference was observed in the total percentage of Vδ2 cells. Contrary to our initial hypothesis, the impact of CLL burden on CD226 and TIGIT expression was lower than anticipated. The former tends to be lower in more advanced disease. Finally, a strong upregulation of CD155 (PVR) was noted on CLL-derived B cells when compared to healthy B cells. CONCLUSIONS: Chronic lymphocytic leukemia regulates the expression of the CD155-CD226/TIGIT axis. Contrary to expectations, the ligand is significantly more affected than the receptors. Nevertheless, the relatively high expression of CD155 and TIGIT makes CLL an interesting target for anti-TIGIT immunotherapy.

Empowering γδ T-cell functionality with vitamin C.

Vitamin C (ascorbic acid) is a potent antioxidant and a cofactor for various enzymes including histone demethylases and methylcytosine dioxygenases. Vitamin C also exerts direct cytotoxicity toward selected tumor cells including colorectal carcinoma. Moreover, vitamin C has been shown to impact immune cell differentiation at various levels including maturation and/or functionality of T cells and their progenitors, dendritic cells, B cells, and NK cells. γδ T cells have recently attracted great interest as effector cells for cell-based cancer immunotherapy, due to their HLA-independent recognition of a large variety of tumor cells. While γδ T cells can thus be also applied as an allogeneic off-the-shelf product, it is obvious that the effector function of γδ T cells needs to be optimized to ensure the best possible clinical efficacy. Here we review the immunomodulatory mechanisms of vitamin C with a special focus on how vitamin C enhances the effector function of γδ T cells. We also discuss future directions of how vitamin C can be used in the clinical setting to boost the efficacy of adoptive cell therapies.

γδ T cell-mediated cytotoxicity against patient-derived healthy and cancer cervical organoids.

Cervical cancer is a leading cause of death among women globally, primarily driven by high-risk papillomaviruses. However, the effectiveness of chemotherapy is limited, underscoring the potential of personalized immunotherapies. Patient-derived organoids, which possess cellular heterogeneity, proper epithelial architecture and functionality, and long-term propagation capabilities offer a promising platform for developing viable strategies. In addition to αß T cells and natural killer (NK) cells, γδ T cells represent an immune cell population with significant therapeutic potential against both hematologic and solid tumours. To evaluate the efficacy of γδ T cells in cervical cancer treatment, we generated patient-derived healthy and cancer ectocervical organoids. Furthermore, we examined transformed healthy organoids, expressing HPV16 oncogenes E6 and E7. We analysed the effector function of in vitro expanded γδ T cells upon co-culture with organoids. Our findings demonstrated that healthy cervical organoids were less susceptible to γδ T cell-mediated cytotoxicity compared to HPV-transformed organoids and cancerous organoids. To identify the underlying pathways involved in this observed cytotoxicity, we performed bulk-RNA sequencing on the organoid lines, revealing differences in DNA-damage and cell cycle checkpoint pathways, as well as transcription of potential γδ T cell ligands. We validated these results using immunoblotting and flow cytometry. We also demonstrated the involvement of BTN3A1 and BTN2A1, crucial molecules for γδ T cell activation, as well as differential expression of PDL1/CD274 in cancer, E6/E7+ and healthy organoids. Interestingly, we observed a significant reduction in cytotoxicity upon blocking MSH2, a protein involved in DNA mismatch-repair. In summary, we established a co-culture system of γδ T cells with cervical cancer organoids, providing a novel in vitro model to optimize innovative patient-specific immunotherapies for cervical cancer.

Prognostic Potential of Galectin-9 mRNA Expression in Chronic Lymphocytic Leukemia.

Galectin-9 (Gal-9), very poorly characterized in chronic lymphocytic leukemia (CLL), was chosen in our study to examine its potential role as a CLL biomarker. The relation of Gal-9 expression in malignant B-cells and other routinely measured CLL markers, as well as its clinical relevance are poorly understood. Gal-9 mRNA expression was quantified with RT-qPCR in purified CD19+ B-cells of 100 CLL patients and analyzed in the context of existing clinical data. Our results revealed the upregulation of Gal-9 mRNA in CLL cells. High Gal-9 mRNA expression was closely associated with unfavorable prognostic markers. In addition, Gal-9 expression in leukemic cells was significantly elevated in CLL patients who did not respond to the first-line therapy compared to those who did respond. This suggests its potential predictive value. Importantly, Gal-9 was an independent predictor for the time to treatment parameters. Thus, we can suggest an adverse role of Gal-9 expression in CLL. Interestingly, it is possible that Gal-9 expression is induced in B-cells by EBV infection, so we determined the patients' EBV status. Our suggestion is that EBV coinfection could worsen prognosis in CLL, partly due to Gal-9 expression upregulation caused by EBV.

Tumor infiltrating lymphocytes and radiological picture of the tumor.

Tumor microenvironment (TME) is a complex entity that includes besides the tumor cells also a whole range of immune cells. Among various populations of immune cells infiltrating the tumor, tumor infiltrating lymphocytes (TILs) are a population of lymphocytes characterized by high reactivity against the tumor component. As, TILs play a key role in mediating responses to several types of therapy and significantly improve patient outcomes in some cancer types including for instance breast cancer and lung cancer, their assessment has become a good predictive tool in the evaluation of potential treatment efficacy. Currently, the evaluation of the density of TILs infiltration is performed by histopathological. However, recent studies have shed light on potential utility of several imaging methods, including ultrasonography, magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT), and radiomics, in the assessment of TILs levels. The greatest attention concerning the utility of radiology methods is directed to breast and lung cancers, nevertheless imaging methods of TILs are constantly being developed also for other malignancies. Here, we focus on reviewing the radiological methods used to assess the level of TILs in different cancer types and on the extraction of the most favorable radiological features assessed by each method.

Changes in the Histological Structure of Adrenal Glands and Corticosterone Level after Whey Protein or Bee Pollen Supplementation in Running and Non-Running Rats.

Due to the many health-promoting properties of bee pollen and whey protein, both products are widely used as dietary supplements. According to these reports on their health-promoting properties, the aim of our study is to assess whether these products can influence the structure and function of the adrenal glands in rats. Thirty male Wistar rats were divided into six equal groups. Among them, there were three groups which included non-running rats and three groups which included running rats. Both of these running (n = 3) and non-running (n = 3) groups included non-supplemented (control groups), bee-pollen-supplemented groups, and whey-protein-supplemented groups. After 8 weeks, the rats were decapitated, their adrenal glands were collected, and paraffin slides were prepared. Then, staining according to the standard H&E and Masson's trichrome protocols was performed. Fecal and urine samples were collected prior to the end of the study to measure corticosterone levels. In the group of non-running rats, the consumption of bee pollen was noted to be significantly higher when compared to the group of running rats (p < 0.05). The thickness of the particular adrenal cortex layers was similar among all of the groups (p > 0.05). The statistically significant changes in the microscopic structure of the adrenal glands, especially regarding cell nuclei diameter and structure, as well as the architecture of sinusoids, were observed between the groups. Moreover, urine corticosterone concentrations were found to vary between all of the analyzed groups (p < 0.05). These results indicate that both bee pollen and whey protein have limited stress-reducing potential.

Effect of immunostimulation with bacterial lysate on the clinical course of allergic rhinitis and the level of γδT, iNKT and cytotoxic T cells in children sensitized to grass pollen allergens: A randomized controlled trial.

Background: There are many drugs for allergic rhinitis (AR), however, these drugs show variable clinical effectiveness and some side effects. Therefore, new methods of AR pharmacotherapy are being sought. Objectives: The objectives of this study were to evaluate the efficacy of polyvalent mechanical bacterial lysate (PMBL) therapy in improving the clinical course of grass pollen-induced AR (seasonal AR, SAR) in children and its effect on changes in the blood level of the γδT, iNKT and cytotoxic T cell subsets. Methods: Fifty children with SAR were enrolled in this study and were randomly assigned to either the PMBL group or the placebo group. The severity of SAR symptoms was assessed using the total nasal symptom score (TNSS) and visual analogue scale (VAS). During two visits (V1, V2), peak nasal inspiratory flow (PNIF) was measured and peripheral blood was collected for immunological analyses. The study also included 2 telephone contacts (TC1, TC2). Results: The severity of the nasal symptoms of SAR on the TNSS scale was revealed to have a significantly lower impact in the PMBL group vs the placebo group at measuring points TC1 and V2 (p = 0.01, p = 0.009, respectively). A statistically significantly lower mean severity of nasal symptoms of SAR on the VAS scale was recorded for children in the PMBL group compared to the placebo group at measuring points TC1, V2 and TC2 (p = 0.04, p = 0.04, p = 0.03, respectively). The compared groups do not show significant differences in terms of PNIF values at individual measuring points. There were no statistically significant changes in immune variables. For both groups, there was a statistically significant association between the level of Th1-like γδT cells and the severity of SAR symptoms expressed on the TNSS scale (p = 0.03) - the lower the level of Th1-like γδT cells, the higher the TNSS value. Conclusion: Administration of sublingual PMBL tablets during the grass pollen season proves to have a high efficacy in alleviating SAR symptoms in children sensitized to grass pollen allergens. Th1-like γδT cells may be used as potential markers for SAR severity in children. Clinical trial registration: ClinicalTrials.gov, identifier (NCT04802616).

Pro- vs. Anti-Inflammatory Features of Monocyte Subsets in Glioma Patients.

Monocytes constitute a heterogenous group of antigen-presenting cells that can be subdivided based on CD14, CD16 and SLAN expression. This division reflects the functional diversity of cells that may play different roles in a variety of pathologies including gliomas. In the current study, the three monocyte subpopulations: classical (CD14+ CD16+ SLAN-), intermediate (CD14dim CD16+ SLAN-) and non-classical (CD14low/- CD16+ SLAN+) in glioma patients' peripheral blood were analysed with flow cytometry. The immune checkpoint molecule (PD-1, PD-L1, SIRPalpha, TIM-3) expression along with pro- and anti-inflammatory cytokines (TNF, IL-12, TGF-beta, IL-10) were assessed. The significant overproduction of anti-inflammatory cytokines by intermediate monocytes was observed. Additionally, SLAN-positive cells overexpressed IL-12 and TNF when compared to the other two groups of monocytes. In conclusion, these results show the presence of different profiles of glioma patient monocytes depending on CD14, CD16 and SLAN expression. The bifold function of monocyte subpopulations might be an additional obstacle to the effectiveness of possible immunotherapies.

Prognostic Value of the miR-17~92 Cluster in Chronic Lymphocytic Leukemia.

The aim of this study was to investigate the expression of miR-17∼92 cluster members in chronic lymphocytic leukemia (CLL) patients. Six microRNAs (miRNAs)-miR-17, miR-18a, miR-19a, miR-19b-1, miR-20a, and miR-92a-1-very poorly characterized in CLL patients, were chosen for the study to consider their possible role as cancer biomarkers. It is currently unclear to which extent miR-17~92 expression is related to other routinely measured CLL markers, and whether the findings can be of any clinical significance. To achieve this goal, we report the expression levels of these miRNAs detected by RT-qPCR in purified CD19+ B lymphocytes of 107 CLL patients and correlate them with existing clinical data. The study provides new evidence regarding the heterogeneity of miR-17~92 cluster members' expression in CLL patients. Higher miR-17-5p expression was associated with unfavorable prognostic factors (i.e., 17p and 11q deletions, CD38 and ZAP-70 expression). On the other hand, miR-19a, miR-20a, and miR-92a-1 negatively correlated with these adverse factors. The presence of del(13q) as a sole aberration was associated with a significantly lower miR-17-5p as well as higher miR-19a-3p and miR-92a-1-5p expression compared to patients carrying unfavorable genetic aberrations. Particularly, miR-20a could be considered an independent favorable prognostic factor. In a multivariate analysis, high miR-20a expression remained an independent marker predicting long TTT (time to treatment) for CLL patients.

Can Galectin-3 Be a Novel Biomarker in Chronic Lymphocytic Leukemia?

Galectin-3's (Gal-3) effect on the pathogenesis of chronic lymphocytic leukemia (CLL) has not yet been extensively studied. The present study aims to analyze the potential role of Gal-3 as a prognostic biomarker in CLL patients. The Gal-3 expression was evaluated in CLL cells with RT-qPCR and flow cytometry. Due to the unclear clinical significance of soluble Gal-3 in CLL, our goal was also to assess the prognostic value of Gal-3 plasma level. Because cell survival is significantly affected by the interaction between Gal-3 and proteins such as Bcl-2, the results of Gal-3 expression analysis were also compared with the expression of Bcl-2. The results were analyzed for known prognostic factors, clinical data, and endpoints such as time to first treatment and overall survival time. Our research confirmed that Gal-3 is detected in and on CLL cells. However, using Gal-3 as a potential biomarker in CLL is challenging due to the significant heterogeneity in its expression in CLL cells. Moreover, our results revealed that Gal-3 mRNA expression in leukemic B cells is associated with the expression of proliferation markers (Ki-67 and PCNA) as well as anti-apoptotic protein Bcl-2 and can play an important role in supporting CLL cells.

Signal strength of STING activation determines cytokine plasticity and cell death in human monocytes.

The cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway is a cytosolic sensor of microbial and host-derived DNA and plays a key role in innate immunity. Activation of STING by cyclic dinucleotide (CDN) ligands in human monocytes induces a type I interferon response and production of pro-inflammatory cytokines associated with the induction of massive cell death. In this study we have re-evaluated the effect of signal strength of STING activation on the cytokine plasticity of human monocytes. CDN (2'3'c-GAMP) and non-CDN (diABZI, MSA-2) STING ligands in the range of EC50 concentrations (15 µM 2'3'c-GAMP, 100 nM diABZI, 25 µM MSA-2) induced IFN-ß, IP-10, and large amounts of IL-1ß and TNF-α, but no IL-10 or IL-19. Interestingly, LPS-induced production of IL-10 and IL-19 was abolished in the presence of diABZI or MSA-2, whereas IL-1ß and TNF-α were not inhibited. Surprisingly, we observed that tenfold lower (MSA-2, i.e. 2.5 µM) or 100-fold lower (diABZI, i.e. 1 nM) concentrations strongly stimulated secretion of anti-inflammatory IL-10 and IL-19, but little of IL-1ß and TNF-α. Induction of IL-10 was associated with up-regulation of PRDM1 (Blimp-1). While cytokine secretion stimulated by the higher concentrations was accompanied by apoptosis as shown by cleavage of caspase-3 and PARP-1, the low concentrations did not trigger overt cell death yet induced cleavage of gasdermin-D. Our results reveal a previously unrecognized plasticity of human monocytes in their signal strength-dependent production of pro- versus anti-inflammatory cytokines upon STING activation.

Promising Immunomodulatory Effects of Bacterial Lysates in Allergic Diseases.

In light of an escalating prevalence of allergic disorders, it is crucial to fully comprehend their pathophysiology and etiology. Such knowledge would play a pivotal role in the search for new therapeutic approaches concerning not only diseases' symptoms, but also their underlying causes. The hygiene hypothesis indicates a high correlation between limited exposure to pathogens in early childhood and the risk of developing allergic disorders. Bearing in mind the significance of respiratory and digestive systems' mucous membrane's first-line exposure to pathogens as well as its implications on the host's immune response, a therapy targeted at aforesaid membranes could guarantee promising and extensive treatment outcomes. Recent years yielded valuable information about bacterial lysates (BLs) known for having immunomodulatory properties. They consist of antigen mixtures obtained through lysis of bacteria which are the most common etiologic agents of respiratory tract infections. They interact with dendritic cells located in the mucous membranes of the upper respiratory tract and the gastrointestinal tract by toll-like receptors. The dendritic cells present acquired antigens resulting in innate immune response development on the release of chemokines, both stimulating monocytes and NK cells maturation and promoting polymorphonuclear neutrophil migration. Moreover, they influence the adaptive immune system by stimulating an increase of specific antibodies against administered bacterial antigens. The significance of BLs includes not only an anti-inflammatory effect on local infections but also restoration of Th1/Th2 balance, as demonstrated mainly in animal models. They decrease Th2-related cytokine levels (IL-4, IL-13) and increase Th1-related cytokine levels (IFN-γ). The reestablishment of the balance of the immune response leads to lowering atopic reactions incidence which, in addition to reduced risk of inflammation, provides the alleviation and improvement of clinical manifestations of allergic disorders. In this review, we hereby describe mechanisms of BLs action, considering their significant immunomodulatory role in innate immunity. The correlation between local, innate, and adaptive immune responses and their impact on the clinical course of allergic disorders are discussed as well. To conclude our review, we present up-to-date literature regarding the outcomes of BLs implemented in atopic dermatitis, allergic rhinitis, and asthma prevention and treatment, especially in children.

PECAM-1 Is Down-Regulated in γδT Cells during Remission, but Up-Regulated in Relapse of Multiple Sclerosis.

Introduction. PECAM-1 and NKRP1A are both involved in the vascular transmigration of T lymphocytes. Vascular transmigration is a crucial process in multiple sclerosis pathogenesis. Methods and aim. The current paper presents an analysis of PECAM-1 and NKRP1A expression on γδ T cells. Expression of PECAM-1 and NKRP1A on subsets of γδ T cells was performed with flow cytometry. Results. Based on the flow cytometry data, PECAM1 was slightly differentially modulated on γδ T cells-it was up-regulated during relapse, but down-regulated during remission. Moreover, a significant downregulation of CD3 expression was noted on γδ T cells from MS patients, most notably during relapse. Conclusions. This may be a sign of the overall activation of γδ T cells in the course of multiple sclerosis.

Changes in Histological Structure, Interleukin 12, Smooth Muscle Actin and Nitric Oxide Synthase 1. and 3. Expression in the Liver of Running and Non-Running Wistar Rats Supplemented with Bee Pollen or Whey Protein.

Introduction: Bee pollen is a natural substance obtained from flowers by bees. It is a rich source of protein, vitamins and minerals. It can be used as a dietary supplement. Bee pollen has been investigated for the treatment of some diseases with promising potential. It can be helpful in supportive therapy for dyslipidemia, metabolic syndrome, diabetes type 2, as well the prevention and control of coronary heart disease and myocardial infarction. Whey protein is a rich source of amino acids. It is a basic dietary supplement for many athletes, both professional and amateur. It stimulates muscle growth and provides nutrition for cachectic patients. Aim of the study: The objective of the study was to assess the impact of dietary supplementation of bee pollen or whey protein on the Wistar rat liver histological structure and expression of interleukin 12, smooth muscle actin and nitric oxide synthases among running and non-running rats. Material and methods: Thirty male Wistar rats were divided into six equal groups, three running and three non-running. Among both there was one control, one supplemented with bee pollen and one receiving whey proteins. After 8 weeks, all animals were decapitated and their livers were collected. Five micrometer thick slides were prepared and used for classical histological staining and immuno-histochemistry. ImageJ image analysis software was used to measure optical density and immunohistochemistry profile coverage. Results: Among all groups, morphology of liver was similar. In the running control group, expression of interleukin-12 (IL-12) was decreased as well as expression of endothelial nitric oxide synthase (eNOS) in a group of bee pollen supplemented rats. No significant changes in α- smooth muscle actin (α-SMA) expression was observed. Conclusions: Bee pollen is proving to be a questionable choice for athletes as an alternative to whey protein. Bee pollen supplementation affects hepatocyte cellular activity and has hepatoprotective effects. Whey protein performs worse in this regard. Lower antioxidant properties were found in groups supplemented with bee pollen than with whey protein.

Reduced Percentage of CD14dimCD16+SLAN+ Monocytes Producing TNF and IL-12 as an Immunological Sign of CLL Progression.

Monocytes are one of the least studied immune cells with a potentially important role in the pathogenesis of chronic lymphocytic leukemia (CLL). Nevertheless, data regarding the role of subpopulations of monocytes in the CLL microenvironment are still limited. For the very first time, this study presents an assessment of monocyte subsets divided according to SLAN and CD16 expression in CLL patients. The study involved 70 freshly diagnosed CLL patients and 35 healthy donors. Using flow cytometry, monocyte subpopulations were assessed among PBMCs. CD14+ monocytes can be divided into: "classical" (CD14+CD16-SLAN-), "intermediate" (CD14+CD16+SLAN-) and "non-classical" (CD14dimCD16+SLAN+). In our study, we noted an increased percentage of non-classical monocytes with intracellular expression of TNF and IL-12. On the other hand, among the intermediate monocytes, a significantly higher percentage of cells synthesizing anti-inflammatory IL-10 was detected. The percentage of CD14dimCD16+SLAN+ monocytes producing TNF and IL-12 decreased with the stage of CLL and inversely correlated with the expression of the prognostic factors ZAP-70 and CD38. Moreover, the percentage of CD14dimCD16+SLAN+ monocytes producing TNF and IL-12 was lower in CLL patients requiring treatment. This may indicate the beneficial effect of non-classical monocytes on the anti-tumor response.

Stimulatory and inhibitory activity of STING ligands on tumor-reactive human gamma/delta T cells.

Ligands for Stimulator of Interferon Genes (STING) receptor are under investigation as adjuvants in cancer therapy. Multiple effects have been described, including induction of immunogenic cell death and enhancement of CD8 T-cell mediated anti-tumor immunity. However, the potential effects of STING ligands on activation and effector functions of tumor-reactive human γδ T cells have not yet been investigated. We observed that cyclic dinucleotide as well as novel non-dinucleotide STING ligands diABZI and MSA-2 co-stimulated cytokine induction in Vδ2 T cells within peripheral blood mononuclear cells but simultaneously inhibited their proliferative expansion in response to the aminobisphosphonate Zoledronate and to γδ T-cell specific phosphoantigen. In purified γδ T cells, STING ligands co-stimulated cytokine induction but required the presence of monocytes. STING ligands strongly stimulated IL-1ß and TNF-α secretion in monocytes and co-stimulated cytokine induction in short-term expanded Vδ2 γδ T-cell lines. Simultaneously, massive cell death was triggered in both cell populations. Activation of STING as revealed by TBK1/IRF3 phosphorylation and IP-10 secretion varied among STING-expressing tumor cells. STING ligands modulated tumor cell killing by Vδ2 T cells as analyzed in Real-Time Cell Analyzer to variable degree, depending on the tumor target and time course kinetics. Our study reveals complex regulatory effects of STING ligands on human γδ T cells in vitro. These results help to define conditions where STING ligands might boost the efficacy of γδ T cell immunotherapy in vivo.

The Mysterious Actor-γδ T Lymphocytes in Chronic Lymphocytic Leukaemia (CLL).

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia among adults. It is the clonal expansion of B cells expressing CD19 and CD5. Despite significant progress in treatment, CLL is still incurable. γδ T cells comprise an important subset of the cytotoxic T cells. Although γδ T cells in CLL are dysfunctional, they still can possibly be used for immunotherapy. The current paper reviews our understanding of γδ T lymphocytes in CLL.

IL-15 Is Overexpressed in γδ T Cells and Correlates with Disease Severity in Relapsing-Remitting Multiple Sclerosis.

Interleukin 15 (IL-15) is known to be involved in the pathogenesis of multiple sclerosis (MS). An animal study revealed a distinct subset of IL-15-producing γδ T cells that correlate with disease severity. The aim of the current study was to test whether such a subset is also present in humans and its importance for the pathogenesis of MS. The peripheral blood from 29 patients with relapsing-remitting MS (including 6 relapses) and 22 controls was stained with monoclonal antibodies and analyzed with flow cytometry. The existence of IL-15+ γδ T cells was confirmed. Moreover, the percentage of IL-15+ γδ T is significantly increased in MS patients and correlates with disease severity. Nevertheless, additional functional studies are needed to fully understand the importance of those cells in multiple sclerosis pathogenesis.

NKT and NKT-like Cells in Autoimmune Neuroinflammatory Diseases-Multiple Sclerosis, Myasthenia Gravis and Guillain-Barre Syndrome.

NKT cells comprise three subsets-type I (invariant, iNKT), type II, and NKT-like cells, of which iNKT cells are the most studied subset. They are capable of rapid cytokine production after the initial stimulus, thus they may be important for polarisation of Th cells. Due to this, they may be an important cell subset in autoimmune diseases. In the current review, we are summarising results of NKT-oriented studies in major neurological autoimmune diseases-multiple sclerosis, myasthenia gravis, and Guillain-Barre syndrome and their corresponding animal models.

γδ T Lymphocytes in Asthma: a Complicated Picture.

A minor subset (approximately 5%) of peripheral T cells has their TCR build up from γ and δ chains instead of α and ß-those are the γδ T lymphocytes. They can be functionally divided into subsets, e.g., Th1-, Th2-, Th9-, Th17-, Tfh-, and Treg-like γδ T cells. They share some specifics of both innate and adaptive immunity, and are capable of rapid response to a range of stimuli, including some viral and bacterial infections. Atopic diseases, including asthma, are one of major health-related problems of modern western societies. Asthma is one of the most common airway diseases, affecting people of all ages and having potential life-threatening consequences. In this paper, we review the current knowledge about the involvement of γδ T cells in the pathogenesis of asthma and its exacerbations. We summarize both the studies performed on human subjects as well as on the murine model of asthma. γδ T cells seem to be involved in the pathogenesis of asthma, different subsets probably perform opposite functions, e.g., symptom-exacerbating Vγ1 and symptom-suppressing Vγ4 in mice model of asthma.