[Subpopulations of Regulatory T-lymphocytes in the Peripheral Blood of Patients with Rheumatoid Arthritis].

BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory rheumatic disease associated with a dysfunction of the T cell-mediated tolerance and leading to the disability of working population. The regulatory CD4' T cells play an important role in the regulation of autoimmunity and can suppress immune responses. With that, there is no consensus on the content of these lymphocytes and their role in the pathogenesis of RA. Objective: The aim of the study was to assess the content ofperipheral blood regulatory Tcells (Treg) according to the expression of membrane markers CD4, CD25, CD127 and intracellular FOXP3 marker, as well as the expression of two functional molecules (CTLA-4 and CCR4) in Treg cells of patients with RA. METHODS: Peripheral blood samples of RA patients (median age 65,5 years [54;68,3) and healthy controls (median age 58 years [44; 66]) were analyzed. Cell count and the expression level of molecules were assessed by flow cytometry. RESULTS: Peripheral blood samples of 36 RA patients and 20 healthy donors were analyzed. The number of the cells with Treg-associated phenotypes CD4⁺CD25hi and CD4⁺CD25hiCD127low/⁻ was higher in RA patients in comparison with healthy donors. Increased levels of RA CD4⁺ T cells expressing FOXP3 were also observed. This may be due to increasing in the number of CD4⁺FOXP3⁺CD25⁻ lymphocytes, whereas the content of RA CD4⁺FOXP3⁺CD25⁺ Treg cells was at the level of the control. The expression of the functional molecule CTLA-4 in Treg cells of patients with RA was not different from the control, while the expression level of the chemokine receptor CCR4 which provides migration of lymphocytes at sites of inflammation and barrier tissues was significantly increased in RA patients. CONCLUSION: Increase in the levels of certain Treg-associated lymphocyte populations were detected in peripheral blood of RA patients. During the natural course of RA, alterations in the level of the chemokine receptor CCR4 might indicate the enhanced lymphocyte migration.

[Circulating regulatory T-cells and changes in the subpopulation composition of lymphocytes in colorectal cancer patients].

Data on the frequency of peripheral Treg cells, their functional activity, as well as their relationship to changes in characteristics of cellular immunity in patients with colorectal cancer (CRC, n=42) and healthy donors (n=34) are presented in the article. Assessment of the expression of molecular markers of lymphocytes was performed by multicolor flow cytometry. It was shown that the number of these cells is significantly increased in CRC patients (p<0,05). Probably CD4+CD25+FOXP3+ Treg cells may play a more substantial role in the periphery during the initial period of tumor formation, whereas CD8+FOXP3+ Treg cells are important in the later stages of the disease. In CRC patients, the increase of the functional activity of Treg cells (CD4+CD25+CD127lo/') on the expression of inhibitory molecules CTLA-4 and the marker of cell proliferation Ki-67 was observed. In patients with CRC, the frequency of peripheral Treg cells and the expression level of CTLA-4 were inversely correlated with the number of CD3+CD4+ T-helper cells.

[Alterations of lymphocyte subsets and indicators of immune suppression in patients with acute pancreatitis].

THE AIM OF STUDY: Assessment of changes in lymphocyte number and some indicators of the immune suppression (frequency of regulatory T cells (Treg), the level of expression of CTLA-4 (cytolytic T lymphocyte-associated antigen 4) and interleukin (IL)-10) in patients with acute pancreatitis (AP). MATERIALS AND METHODS: Peripheral blood samples of 21 patients with AP (including 11 patients with pancreatic necrosis (PN)) were studied for analysis of lymphocyte subsets and 11 blood samples of healthy donors were estimated as control. Evaluation of the expression of molecules of lymphocytes was carried out by flow cytometry. RESULTS: It was found that percentage of CD3+ T cells and their subpopulation of CD4+ T-helper cells in patients with AP were decreased as compared to the control group. Substantial changes were observed in patients with PN: together with decrease in the number of T cells, CD19+ B cells and CD4+ CD25+ activated T-helper cells were also reduced, and the percentage of CD8+ T cells was higher. The immunoregulatory index (CD4+/CD8+) was lower in the group of patients, than in control group. The frequency of Treg cells (CD4+ CD25hi and CD4+ CD25+ CD127lo) was higher in patients with AP than in the control. The expression level of the inhibitory molecule CTLA-4 in the subset of CD4+ CD25hi Treg cells in patients with AP was also increased. Moreover, it was found that the expression level of anti-inflammatory cytokine IL-10 was higher in T-helper cells from patients with AP. CONCLUSION: Changes in cellular immunity (especially patients with PN) werefound in patients wish AP. These changes may indicate the possible development of secondary immunodeficiency. This is probably related to the generation of immune suppression, since the values of the investigated parameters (frequency of Treg cells, the expression of CTLA-4 and IL-10) in patients with AP were higher than in controls.

[Declining mitogen-induced polyclonal activity of peripheral blood lymphocytes as an index of immunosuppression involved in different neoplasms].

Regulatory T cells are crucial for maintaining T cell tolerance to-self-antigens and autoimmune process prevention. They are known to be able to cut down in vitro autologous lymphocyte proliferation in mice. It is suggested that their increased levels are responsible for immunosuppression in human tumor growth. Our investigation was concerned with identifying the extent of mitogen-stimulated T- and B-cell concentration changes as well as phenotypic variation in peripheral blood lymphocyte level in lung, stomach, breast and colorectal cancer. It was found that malignancy involves reduced mitogen (PHA, ConA, PWM)-stimulated lymphocyte proliferation and enhanced peripheral blood CD25+-cell concentration which should be accounted for by regulatory T cell increase. However, both the extent of proliferation changes and CD25+-lymphoid cell concentration considerably depended on tumor localization, which might have an indicator of a varying degree of immunosuppression involved in different neoplasms.

[Expression of lymphocyte activation markers in patients with gastrointestinal tumors at different stages].

Patients with gastrointestinal tumors revealed relatively high levels of activated lymphocytes. CD25 expression at later stages was much higher than at earlier ones (I-II). A relationship between CD25, CD71 and CD95 expression was established for metastatic spread of gastrointestinal tumors as well as a correlation between CD71 and CD98 expression for favorable course. A distinct activation phenotype can be identified for peripheral blood lymphocytes in burgeoning tumor which should be taken into account in prognosis.

Expression of surface lymphocyte markers in various courses of gastrointestinal tumors.

Expression of activation antigens increased in patients with gastrointestinal tumors of various clinical courses. The count of CD25+ and CD71+ lymphocytes was high in patients with favorable course of non-progressive tumors. The increase in the expression of activation markers probably reflects adequate functional activity of the immune system in patients with tumors.

[Phenotype of peripheral blood lymphocytes in patients with lung cancer]. / Izuchenie fenotipa limfotsitov perifericheskoi krovi u bol'nykh rakom legkogo.

The expression of surface markers of blood lymphocytes was studied in 32 lung cancer patients. Tumor process involved enhanced expression of the activation markers CD25, CD71 and HLA-DR as well as differentiation antigens CD4, CD8, CD22 and CD16. The expression of the markers was higher than in control, irrespective of stage, localization and histological pattern of tumor. It is suggested that increased expression of surface markers should be accounted for by tumor-induced suppression of the immune system in lung cancer.

Distribution of digestive enzyme activities along intestine in blue fox, mink, ferret and rat.

The activities of amylase, total proteases, monoglyceride lipase, glycyl-leucine dipeptidase and sucrase were investigated in mucosa from five consecutive parts of small intestine in blue fox, mink, ferret and rat. In comparison with rats, the activity gradient of carbohydrates and TPA in mucosa of predatory animals was shifted in the distal direction. The distribution of dipeptidase and monoglyceride lipase along the intestine was similar enough in all animals: the first was exemplarily the same all along the gut, while the second slightly decreased in a distal direction.

[The enzyme topography of the small intestine in Arctic foxes and mink]. / Topografiia fermentov tonkoi kishki u pestsov i norok.

High level of activity of some digestive enzymes in the distal part of the intestine is characteristic for predatory animals. The role of spatial redistribution of the enzyme activity during the process of dietary adaptation, is discussed.

[The effect of phenamine and caffeine on the ability to extrapolate in rats]. / Vliianie fenamina i kofeina na sposobnost' k ékstrapoliatsii u krys

Solution of an extrapolation problem was studied on 28 albino rats (Way strain and laboratory population) and 68 hybrids (the first generation) of wild and laboratory rats in experiments with a screen--the search of food after the disappearance of the food stimulus from the animal's sight. Administration of caffeine (20 mg/kg) and d,l-amphetamine (0.1 mg/kg), though not changing the share of correct solutions, diminishes the number of "refusals" to solve it. Increased motor activity and diminished emotionality of the rats due to administration of the drugs, recorded in an open field test, are likely to cause a decrease in the number of refusals. Administration of d,l-amphetamine facilitates the process of conditioning which contributes to the greater number of positive solutions of the repeatedly presented task.