The biological activity of the multifunctional cytokine interleukin-1 (IL-1) is mediated by its receptors. The aim of this study was to determine if an association exists between single nucleotide polymorphisms (SNPs) in the IL-1 type 1 and 2 receptor genes (IL1R1 and IL1R2) and the expression level of membrane-bound IL1Rs on subpopulations of mononuclear cells or serum levels of soluble IL-1 receptors. It was observed that healthy individuals with the genotype TT in SNP rs2234650:C.T had a lower percentage of intact CD14 1 monocytes expressing IL1R1 on their surface. The SNP rs4141134:T.C in IL1R2 has also been associated with the percentage of intact CD3 1 T cells expressing IL1R2. Keywords: interleukin-1; membrane-bound receptor; SNPs; soluble receptor INTRODUCTION Interleukin-1 (IL-1) is a cytokine involved in a wide range of physiological processes, including having a central role in the regulation of acute and chronic inflammation. 1,2 The biological effects of IL-1 (IL-1a and IL-1b) are achieved by the binding of the cytokine to the membrane-bound IL-1 type 1 receptor (IL1R1). 3,4 IL1R1 is a glycoprotein with a molecular mass of 80 kDa that is predominantly expressed on endothelial cells, smooth muscle cells, epithelial cells, hepatocytes, fibroblasts, keratinocytes, epidermal dendritic cells and T lymphocytes. 5 IL-1 binding to the extracellular domain of IL1R1 promotes the recruitment of the IL-1 receptor accessory protein, which leads to signal transduction mediated by the cytoplasmic domains of IL1R1 and IL1R2 receptors. 6 The IL-1 type 2 receptor (IL1R2) is unable to initiate signaling and only acts as a 'decoy' receptor. 3,7 IL1R2 is a glycoprotein with a molecular mass of 60 kDa that is expressed on monocytes, neutrophils, T and B lymphocytes. 8,9 Studies have also provided evidence for the existence of soluble receptors for

Background: Erythroid nuclear cells (ENC) of the bone marrow (BM) have not previously been considered as important producers of wide spectrum of haemo-and immunoregulatory cytokines. The aim of the current work was to confirm the production of the main hemo-and immunoregulatory cytokines in human ENC from BM.

Minimal residual disease remaining after resection of primary tumors can lead to tumor recurrence and metastasis, increasing mortality and morbidity rates among cancer patients. Thus, there is a need for new technologies for recognition and elimination of single cancer cells remaining in a patient's body after radiation therapy, chemotherapy, or surgical resection. Effector CD8 + T cells, also commonly known as cytotoxic T lymphocytes (CTLs), play a key role in antitumor cellular immunity and, when properly activated, are able to effectively destroy tumor cells. The aims of this study were to obtain CD8 + CTLs specific for the HER2/neu epitopes E75 and E88 and to assess the cytotoxic activity and composition of these cells in terms of the distribution of memory T-cell subsets. We obtained HER2-specific CD8 + T cells and assessed T cell subset distribution among them including naive T cells (T N ), central memory T cells (T CM ), effector memory T cells (T EM ), stem cell-like memory T cells (T SCM ) and terminally-differentiated T cells (T EMRA ) via eight-color flow cytometry. HER2-specific CTLs were largely (~40–50%) represented by T SCM cells, a population capable of mounting pronounced antitumor immune responses due to a combination of effector function and self-maintenance. In comparison with activated peripheral blood mononuclear cells (PBMCs) and bulk CD8 + T cells, HER2-specific CTLs exhibited greater cytotoxicity against the HER2-expressing human breast adenocarcinoma cell line MCF-7 and produced higher levels of IFN-γ in response to tumor cells. We also showed the presence of HER2-specific CTLs in healthy individuals and increase in them in HER2-positive breast cancer patients. Collectively, our results suggest that HER2-specific CD8 + T cells isolated using this approach could be used for adoptive T-cell transfer to eliminate tumor cells and prevent metastasis and relapse in patients with HER2-overexpressing cancers.

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The level of TNF receptors on various cells of immune system and its association with the gene polymorphism were investigated. Determining the levels of membrane-bound TNFα receptors on peripheral blood mononuclear cells (PBMCs) was performed by flow cytometry using BD QuantiBRITE calibration particles. Soluble TNFα receptor (sTNFRs) levels were determined by ELISA and genotyping was determined by PCR-RFLP. Homozygous TT individuals at SNP −609G/T TNFRI (rs4149570) showed lower levels of sTNFRI compared to GG genotype carriers. Homozygous carriers of CC genotype at SNP −1207G/C TNFRI (rs4149569) had lower expression densities of membrane-bound TNFRI on intact CD14+ monocytes compared to individuals with the GC genotype. The frequency differences in the CD3+ and CD19+ cells expressing TNFRII in relation to SNP −1709A/T TNFRII (rs652625) in healthy individuals were also determined. The genotype CC in SNP −3609C/T TNFRII (rs590368) was associated with a lower percentage of CD14+ cells expressing TNFRII compared to individuals with the CT genotype. Patients with rheumatoid arthritis had no significant changes in the frequencies of genotypes. Reduced frequency was identified for the combination TNFRI −609GT + TNFRII −3609CC only. The polymorphisms in genes represent one of cell type-specific mechanisms affecting the expression levels of membrane-bound TNFα receptors and TNFα-mediated signaling.