In present review article, an effort is undertaken to consolidate current opinions on the most significant surface antigens of immunocompetent cells, and to evaluate their relative roles in regulation of cellular homeostasis and development of pathological conditions.

Incidence of different types of dislipoproteinemias (DLPs) and a balance between apoptosis and
proliferation of lymphocytes were studied in males exhibiting initial manifestations of cerebral blood flow
insufficiency (ICBI). In general, high intensity of lymphocyte activation was revealed in patients with ICBI,
with amplified proliferative potential demonstrable in this group. We have also shown a trend to increased
numbers of T and B lymphocytes expressing antiapoptogenic bcl-2 protein. The changes in apoptosis and cell
proliferation intensity were more pronounced in IIA and IIB types of DLP. In these groups, unidirectional
changes of FasR expression were observed. However, the parameters reflecting readiness to apoptosis were
changed multidirectionally. Cholesterol and oxysterols transported to the cells under excessive dyslipidemia
may influence activities of transcription factor genes (bcl-2, Fas-regulatory gene (TDAG51), thus, probably,
causing an imbalance between cellular proliferation and apoptosis.

The aim of this work was to study an opportunity of coordinated expression of PAX-5 and STAT6 in bronchial asthma (BA) development. 35 healthy controls, 83 patients with allergic bronchial asthma (ABA) and 63 patients with nonallergic bronchial asthma (NABA) o different severity were observed. To evaluate PAX- 5 and β-actin mRNA levels, a reverse transcription-PCR with endpoint detection was applied. To determine STAT6 and pSTAT6 protein levels, ECL Western blotting protocols (Amersham) was used. A negative correlation was revealed between РАХ-5 and STAT6 mRNA expression levels in control group and in ABA. In NABA patients, the appropriate correlations were nonsignificant. Expression of РАХ-5 mRNA in ABA with normal IgE levels showed a significant negative correlation with that of STAT6. Meanwhile, expression levels of active pSTAT6 form in patients with high IgE and eosinophilia did negatively correlate with РАХ-5 mRNA expression. In ABA, effects of IL-4 caused a more significant decrease of РАХ-5 mRNA as compared with those in control group. The strongest negative correlation between РАХ-5 mRNA expression and STAT6 levels was revealed in groups with higher levels of mRNA РАХ-5 and lower levels of STAT6. The revealed negative correlations between STAT6 levels and РАХ-5 mRNA expression suggest that STAT6 may inhibit PAX-5 transcription in ABA group, thus, probably, promoting differentiation of B cells into plasma cells.

We have performed a comparative analysis of allostimulatory, Th1/Th2-stimulatory and
tolerogenic activities of dendritic cells (DCs) derived from healthy donors (n = 52). The DCs were generated
in vitro with IFN-alpha (IFN-DCs) or IL-4 (IL-4-DCs). It was shown that IL-4-DCs and IFN-DCs did
not differ in their key functional characteristics, i.e., in their ability to stimulate proliferation of T-cells in
response to alloantigens, and to induce generation of T-regulatory cells in mixed leukocyte culture. IFN- and
IL-4-induced DCs possess similar ability of boosting T cells to produce Th1/proinflammatory (IFNγ, IL-2,
IL-1β, TNFα, IL-12, IL-17) and Th2/antiinflammatory cytokines (IL-4, IL-6, IL-10, IL-13), growth factors
(G-CSF, GM-CSF, IL-7) and chemokines (IL-8, MIP-1β). Nevertheless, IFN-DCs have more pronounced
stimulatory effect upon Th1 and Th2 cells, thus manifesting as a significantly higher IFNγ, IL-5 and MIP-1β
production. IFN-DCs were characterized by more prominent ability to activate Th1-cells, and by moderate
Th2-stimulatory activity, which is absent in IL-4-DCs. These data strongly suggest that IFN-DCs may present
a quite promising cellular tool for development of therapeutic vaccines aiming to induce/enhance the immune
response.

We studied effects of estriol (E3), at the doses corresponding to the I and III trimesters of pregnancy,
upon expression of functional markers on T-regulatory (Treg) and Th17-producing (Th17) lymphocytes, as
well as the production of relevant cytokines by the cells of patients with multiple sclerosis (MS), as compared
with healthy donors. It was found that the levels of CD4+FoxP3+CTLA-4+ (Treg) lymphocytes in MS patients
were initially lower than those of healthy donors. Percentages of CD4+RORγt+IL-17A+ (Th17) lymphocytes
did not significantly differ from those in healthy donors, still showing a tendency for increase. Baseline levels
of IL-17 and IL-6 in cell culture supernates of MS patients were higher than in healthy donors, along with
reduced contents of the anti-inflammatory IL-10 cytokine. Percentage of Tregs was increased under the
influence of estriol, whereas Th17 proportion was diminished. These hormonal effects upon lymphocytes
were reproducible both for healthy donors, and MS patients. Moreover, estriol stimulated IL-10 production
and inhibited secretion of IL-6 and IL-17. Therefore, a sufficient release of MS symptoms observed during
pregnancy may be explained by influence of estriol, thus extending opportunities for rational use of this steroid
hormone in MS treatment

Decreased production of blocking factors (BF) is a common manifestation of immune dysfunction in women with recurrent spontaneous abortions (RSA), and this disorder may be corrected by lymphocyte immunotherapy performed with paternal lymphocytes (LIT). Our previously data show, in a half of RSA cases, BF deficiency is not associated with a reduced MLC response, being detected not only in RSA, but also in primary infertility of unknown origin. In this work we have investigated the effect of LIT upon BF activity and evaluated clinical efficacy of immunotherapy in women with RSA and primary unexplained infertility, taking into account the efficiency of BF production. The lymphocytes immunotherapy was accompanied by the appearance of BF in women with RSA (75%) and in women with primary unexplained infertility (74%). BF were detected at similar frequency in the groups of women with intact and reduced response in MLC. Clinical efficacy (number of births) was – 65.5% in RSA group, and 40% in primary infertility. The rate of successful pregnancy in both groups was shown to be significantly higher in women positive for BF as compared with the BF-negative women, including women with RSA (70% vs 28%) and primary infertility (50 vs 9%). Hence, LIT in BF-negative women is accompanied by enhanced production of blocking factors, thus being associated with improved pregnancy outcomes, both in females with history of RSA, and in women with unexplained infertility

Efficacy and pharmacodynamics of PPARα agonist fenofibrate have been assessed in a controlled study on patients with active rheumatoid arthritis (RA) receiving traditional DMARDs. After 12 weeks of treatment, we observed a significant drop of DAS28 scores, decrease in number of tender and swollen joints, and slower ESR in fenofibrate group (n = 33) as compared with control group (n = 17). Frequency of EULAR and ACR20 responses was 4 times higher in fenofibrate group. Clinical effect was accompanied by decrease in serum immunological markers of atherosclerosis (IL-6 and CRP), diminished total cholesterol and
triglycerides. In summary, PPARα agonists may represent an example of a “hub” treatment for rheumatoid arthritis, with pleiotropic effects directed at inflammatory activity and increased risk of other comorbidites, including atherosclerosis.

Functional characteristics of neutrophils were evaluated in fifty-two patients with severe form of
chronic recurrent furunculosis, i.e., intensity of oxygen- and nitric oxide production, apoptosis rates, NET-
forming properties, as well as phagocytic and bactericidal capacity. We have detected reduced efficiency of
intracellular pathogen killing, accompanied by a suppression of oxygen- and nitric oxide-producing reserve of
neutrophils. A compensatory increase in functional reserve of NET formation activity was also revealed, thus
being a potential extracellular bactericidal mechanism for neutrophils. At the time of the disease exacerbation,
we have found a decreased readiness for both spontaneous and stimulated neutrophil apoptosis.

Determination of etiologic and\or trigger role of herpesvirus infection, immune disorders in development of hemorrhagic vasculitis with renal impairment is useful for optimizing treatment of such patients. Detection of herpes virus activation markers and disorders of immune status in the development of hemorrhagic vasculitis with renal impairment substantiates complex therapeutic schedules including antiviral and immunocorrection drugs. A timely and purposeful antiviral therapy promotes earlier fading of clinical signs typical to hemorrhagic vasculitis. A long-lasting activation of humoral immune system in combination with urinary syndrome suggests a higher risk of immune nephropathy progression, thus requiring long-term
monitoring and implementation of appropriate therapy.