Vol 22, No 1 (2019)

Long after the onset of chronic radiation exposure with predominant irradiation of red bone marrow (mean exposure dose was 0.89±0.09 Gy, individual dose range was 0.09–1.96 Gy) in individuals with increased level of TCR-gene mutated T-lymphocytes a dose-dependent increase in the number of peripheral blood CD3+CD16+CD56+-lymphocytes, lysosomal activity of neutrophils, lymphocyte necrosis intensity as well as serum IL-1α levels were noted. It is assumed that these changes could be immune response to increase in the mutation frequency (including TCR-mutations) in the cells of individuals exposed at a wide dose-range.

Hematopoietic stem cells transplantation of (HSCT) from the related or unrelated donor is used as a treatment for hematopoietic system malignancies. However, transplantation triggers an immune response of the donor cells to the recipient’s antigens. The response to the healthy tissues is called a graft versus host reaction (GVHD), and the response to the hematopoietic tissue in the context of malignant disease is called a graft versus leukemia (GVL) eff ect. The development of GVL reactivity is a favorable consequence of transplantation, since it eliminates residual tumor cells and prevents the relapse. It was demonstrated that immune response arises towards polymorphic peptides, presented in the molecules of the major histocompatibility complex (HLA). Such peptides are derived from the proteasomal degradation of proteins expressed from the genes with non-synonymous single nucleotide polymorphisms and are referred to as minor histocompatibility antigens (MiHA). Studying the structure of T- cell receptor (TCR) repertoires that recognize MiHAgs can help identify the mechanisms for the formation of the alloreactive response and is important for predicting the antigen of alloreactive clones with unknown specificity. In this article the genetic sequences encoding T-cell receptors specific to the HA-2 minor antigen were determined and analyzed in silico. We found the predominant use of the V21 and J42 segments in the formation of the CDR3 region of the α-chain and the presence of the V7-8 segment in most CDR3 β-chain regions, which indicates the existence of a conservative motif responsible for recognizing the HA-2 antigen.

Neutrophilic granulocytes (NG) with different receptor equipment are heterogeneous subpopulations that have differences in their biological properties and role in the pathogenesis of immune diseases. In result of research we obtained new data on the phenotypic features of NG subpopulations carrying the CD64, CD32, CD16 and CD11b molecules in newborns and children compared to the group of adult healthy individuals. It has been established that in the peripheral blood of healthy full-term newborns, conditionally healthy children of different age and conditionally healthy adults there are two main subpopulations of circulate NG – major with СD64–CD16+CD32+CD11b+ phenotype and minor СD64+CD16+CD32+CD11b+ phenotype, different receptor expression density noted in both subpopulations. It was shown that each of the studied groups has its own phenotypic profile, possibly optimal for performing NG eff ector functions. In newborns are identified phenotypes СD64–CD16^dimCD32^dimCD11^bbrightNG and СD64^dimCD16^midCD32^bright CD11^bbrightNG, in children 2–4 years old СD64–CD16^brightCD32^dimCD11^bbrightNG and СD64^midCD16^bright CD32^dimCD11^bbright NG, in children 5–9 years old СD64–CD16^midCD32^dimCD11^bdimNG and СD64^dim CD16^brightCD32^midCD11^bdimNG, in conditionally healthy adults СD64–CD16^midCD32^dimCD11^bdimNG and СD64^brightCD16^dimCD32^midCD11^bdimNG. Study shown that the NG of newborns and children of different age groups have a similar expression density of the CD64, CD16, CD32, CD11b receptors in major and minor subpopulations, NG subpopulations of healthy adults are equipped differently. The study of receptors in physiological according to age-related features is necessary for the correct interpretation of the transformation of the phenotype, changes in surface receptors expression in various pathological conditions. 

To search for statistically signifi cant T-cell populations in the diagnosis of multiple sclerosis (MS). The analysis of the absolute content of various subpopulations of T-lymphocytes (T-helpers (Th) and cytotoxic T-cells (Tcyt)) in the peripheral blood of 61 healthy volunteers and 47 patients with MS was carried out using multi-color fl ow cytometry. Based on the expression of diff erentiation markers (CD45RA, CD62L, CD27 and CD28) and eff ector molecules (CD56 and CD57), Th and Tcyt were divided into main populations at diff erent stages of maturation. The following statistically signifi cant populations of T-cells were identifi ed: CD56^–CD57⁺ T-lymphocytes, Em Th, EM3 Tcyt, CD56⁺CD57^– T-lymphocytes, EM2 Tcyt. The signifi cance of these populations was also confi rmed in the calculation of Chi-square statistics. Based on the information received, three groups of T-cell populations were selected. A model for the diagnosis of multiple sclerosis based on the algorithm of K nearest neighbors was built on each group of populations. The accuracy of prediction of the constructed models varies in the range of 0.69–0.90. 

To study the mechanism of action of the GMDP peptide mimetic RN, its eff ect on the expression level of mRNA of the pro-infl ammatory cytokines IL-1β and TNF-α and some molecules involved in the activation of the NF-kB signaling pathway in human leukemic monocyte cells THP-1 was evaluated. For comparison, GMDP itself and its two analogues with well-characterized biological activity, GMDPacid and GMDP-Lys, were used. All compounds demonstrated signifi cant diff erences during the development of the immune response: GMDP-Lys turned out to be the strongest stimulator of the immune response; GMDP-acid to a greater extent enhanced the expression of the p100/p52 subunit (NF-kB2) and to a lesser extent the expression of IL-1β in comparison with GMDP; the peculiarities of peptide RN response were low level of IL-1β production and stimulation of the adapter protein RIP2 of innate immunity NOD2 receptor. All compounds studied are valuable tools for fi nding new ways for immune response correction.