IL-2 and IL-15 are structurally relative cytokines that share two receptor subunits, CD132 (γ(c) chain) and CD122 (β chain). However, the expression pattern and physiological role of IL-2 and IL-15 private receptor α chains CD25 and IL-15Rα, respectively, are strikingly different. CD25, together with CD122 and CD132, forms a trimeric high affinity IL-2 receptor that is expressed and functions on cells acquiring an IL-2 signal. Conversely, IL-15Rα is expressed and binds IL-15 with high affinity per se already in the endoplasmic reticulum of the IL-15 producing cells and it presents IL-15 to cells expressing CD122/CD132 dimeric receptor in trans. Thus, while IL-2 is secreted almost exclusively by activated T cells and acts as a free molecule, IL-15 is expressed mostly by myeloid cells and works as a cell surface-associated cytokine. Interestingly, the in vivo biological activity of IL-2 can be dramatically increased through complexing with certain anti-IL-2 mAbs; such IL-2/anti-IL-2 mAbs immunocomplexes selectively stimulate the proliferation of a distinct population of immune cells, depending on the clone of the anti-IL-2 mAb used. IL-2/S4B6 mAb immunocomplexes are highly stimulatory for CD122(high) populations (memory CD8(+) T and NK cells) and intermediately also for CD25(high) populations (Treg and activated T cells), while IL-2/JES6-1 mAb immunocomplexes enormously expand only CD25(high) cells. Although IL-2 immunocomplexes are much more potent than IL-2 in vivo, they show comparable to slightly lower activity in vitro. The in vivo biological activity of IL-15 can be dramatically increased through complexing with recombinant IL-15Rα-Fc chimera; however, IL-15/IL-15Rα-Fc complexes are significantly more potent than IL-15 both in vivo and in vitro. In this review we summarize and discuss the features and biological relevance of IL-2/anti-IL-2 mAbs and IL-15/IL-15Rα-Fc complexes, and try to foreshadow their potential in immunological research and immunotherapy.

• MeSH
• buňky NK cytologie   účinky léků   imunologie   MeSH
• CD8-pozitivní T-lymfocyty cytologie   účinky léků   imunologie   MeSH
• imunoglobuliny - Fc fragmenty chemie   MeSH
• imunokomplex genetika   imunologie   farmakologie   MeSH
• interleukin-15 genetika   imunologie   farmakologie   MeSH
• interleukin-2 genetika   imunologie   farmakologie   MeSH
• lidé MeSH
• monoklonální protilátky chemie   MeSH
• myši MeSH
• receptor interleukinu-15 - alfa-podjednotka genetika   imunologie   MeSH
• receptor interleukinu-2 - alfa-podjednotka genetika   imunologie   MeSH
• receptory interleukinů - společná gama-podjednotka genetika   imunologie   MeSH
• regulace genové exprese MeSH
• regulační T-lymfocyty cytologie   účinky léků   imunologie   MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

The aim of the study was to examine the relation between polymorphisms and serum levels of selected cytokines (IL-6, IL-13 and IL-15), production of autoantibodies and factors describing rheumatoid arthritis (RA), such as DAS28 and Total Sharp Score. A total of 156 patients with RA according to the ACR criteria, and 200 control subjects were recruited into the study. The measurements of CRP, anti-CCP, the presence of rheumatoid factors (RFs), radiographs of both hands with calculation of Total Sharp Score (TSS) and DAS28 were obtained from all patients with RA. In total, five polymorphisms in genes coding cytokines (IL-6, IL-13 and IL-15) were detected. The levels of these selected cytokines were measured in serum using ELISA method. A significant difference in allele frequencies between patients with RA and controls was observed for IL-15 -267C/T polymorphism. A higher prevalence of heterozygote variants of IL-15 polymorphisms (14035A/T and -267C/T) in the RF IgG- and RF IgA-negative subgroups was observed. Furthermore, the association of polymorphisms in gene for IL-15 with circulating level of IL-15 (14035A/T and 367G/A) and with total RF and Ig-specific RFs (-267C/T) was found. The relation of IL-15 to RFs IgA, IgM, IgG and the measure of DAS28 was proved. The frequency of the T allele of the IL-13 polymorphism -1112C/T was higher in subgroup with faster progression of the disease (TSS/month ≥ 0.1). In conclusion, we present an association of IL-15 gene polymorphisms with the RFs including subtypes (RF, IgG, IgA) underlined by the relation of increased IL-15 levels in circulation to RFs.

• MeSH
• alely MeSH
• autoprotilátky krev   MeSH
• dospělí MeSH
• genetické asociační studie MeSH
• haplotypy MeSH
• imunoglobulin A krev   imunologie   MeSH
• imunoglobulin G krev   imunologie   MeSH
• imunoglobulin M krev   imunologie   MeSH
• interleukin-13 genetika   MeSH
• interleukin-15 genetika   MeSH
• interleukin-6 genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• polymorfismus genetický * MeSH
• progrese nemoci MeSH
• revmatoidní artritida krev   genetika   MeSH
• revmatoidní faktor krev   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The aim of study was to examine relationship among levels of cytokines (IL-6, IL-13, IL-15, TNF-α) and chemokine (IL-8), production of autoantibodies, radiographic progression, and factors describing rheumatoid arthritis (RA). A total of 156 RA patients according to ACR criteria, and 55 control subjects were recruited into study. We observed higher levels of IL-15 within RA patients compared to healthy controls. Correlations among cytokine levels and the measures of rheumatoid factors, anti-CCP, measures of disease activity, and radiographic progression were observed. We conclude that IL-15 level in circulation could serve as one of the biomarkers for RA detection.

• MeSH
• autoprotilátky krev   MeSH
• biologické markery krev   MeSH
• cyklické peptidy imunologie   MeSH
• cytokiny krev   MeSH
• dospělí MeSH
• interleukin-15 krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• progrese nemoci MeSH
• revmatoidní artritida krev   imunologie   radiografie   MeSH
• ROC křivka MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Previous studies from Multhoff and colleagues reported that plasma membrane Hsp70 acts as a tumour-specific recognition structure for activated NK cells, and that the incubation of NK cells with Hsp70 and/or a 14-mer peptide derived from the N-terminal sequence of Hsp70 (TKDNNLLGRFELSG, TKD, aa 450-463) plus a low dose of IL-2 triggers NK cell proliferation and migration, and their capacity to kill cancer cells expressing membrane Hsp70. Herein, we have used flow cytometry to determine the influence of in vitro stimulation of peripheral blood mononuclear cells from healthy individuals with IL-2 or IL-15, either alone or in combination with TKD peptide on the cell surface expression of CD94, NK cell activatory receptors (CD16, NK2D, NKG2C, NKp30, NKp44, NKp46, NKp80, KIR2DL4, DNAM-1 and LAMP1) and NK cell inhibitory receptors (NKG2A, KIR2DL2/L3, LIR1/ILT-2 and NKR-P1A) by CD3+CD56+ (NKT), CD3+CD4+, CD3+CD8+ and CD19+ populations. NKG2D, DNAM-1, LAMP1 and NKR-P1A expression was upregulated after the stimulation with IL-2 or IL-15 alone or in combination with TKD in NKT, CD8+ T cells and B cells. CD94 was upregulated in NKT and CD8+ T cells. Concurrently, an increase in a number of CD8+ T cells expressing LIR1/ILT-2 and CD4+ T cells positive for NKR-P1A was observed. The proportion of CD8+ T cells that expressed NKG2D was higher after IL-2/TKD treatment, when compared with IL-2 treatment alone. In comparison with IL-15 alone, IL-15/TKD treatment increased the proportion of NKT cells that were positive for CD94, LAMP1 and NKRP-1A. The more potent effect of IL-15/TKD on cell surface expression of NKG2D, LIR1/ILT-2 and NKRP-1A was observed in B cells compared with IL-15 alone. However, this increase was not of statistical significance. IL-2/TKD induced significant upregulation of LAMP1 in CD8+ T cells compared with IL-2 alone. Besides NK cells, other immunocompetent cells present within the fraction of peripheral blood mononuclear cells were influenced by the treatment with low-dose interleukins themselves or in combination with hsp70 derived (TKD) peptide.

• MeSH
• B-lymfocyty účinky léků   metabolismus   MeSH
• buňky NK účinky léků   metabolismus   MeSH
• dospělí MeSH
• interleukin-15 farmakologie   MeSH
• interleukin-2 farmakologie   MeSH
• kohortové studie MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• peptidové fragmenty chemie   farmakologie   MeSH
• proteiny tepelného šoku HSP70 chemie   metabolismus   MeSH
• receptory imunologické metabolismus   MeSH
• T-lymfocyty účinky léků   metabolismus   MeSH
• techniky in vitro MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

NK cells represent a potential tool for adoptive immunotherapy against tumors. Membrane-bound Hsp70 acts as a tumor-specific marker enhancing NK cell activity. Using flow cytometry the effect of in vitro stimulation with IL-2 or IL-15 alone or in combination with Hsp70-derived 14-mer peptide (TKD) on cell surface expression of NK activatory receptors (CD16, NKG2D, NKG2C, NKp46, NKp44, NKp30, KIR2DL4, DNAM-1, and LAMP1) and NK inhibitory receptors (NKG2A, KIR2DL2/L3, LIR1/ILT-2, and NKR-P1A) in healthy individuals was studied. Results were expressed as the percentage of receptor expressing cells and the amount of receptor expressed by CD3(-)CD56(+) cellular population. CD94, NKG2D, NKp44, NKp30, KIR2DL4, DNAM-1, LAMP1, NKG2A, and NKR-P1A were upregulated after the stimulation with IL-2 or IL-15 alone or in combination with TKD. KIR2DL2/L3 was upregulated only by IL-15 and IL-15/TKD. Concurrently, an increase in a number of NK cells positive for CD94, NKp44, NKp30, KIR2DL4, and LAMP1 was observed. IL-15 and IL-15/TKD caused also cell number rise positive for KIR2DL2/L3 and NKR-P1A. Cell number positive for NKG2C and NKG2A was increased only by IL-2 and IL-2/TKD. The diverse effect of IL-2 or IL-15 w or w/o TKD on cell surface expression was observed in CD16, NKp46, and LIR1/ILT-2.

• MeSH
• buňky NK účinky léků   metabolismus   MeSH
• diferenciační antigeny T-lymfocytů metabolismus   MeSH
• interleukin-15 farmakologie   MeSH
• interleukin-2 farmakologie   MeSH
• kultivované buňky MeSH
• lektinové receptory NK-buněk - podrodina B metabolismus   MeSH
• lektinové receptory NK-buněk - podrodina C metabolismus   MeSH
• lektinové receptory NK-buněk - podrodina K metabolismus   MeSH
• leukocyty mononukleární účinky léků   metabolismus   MeSH
• lidé MeSH
• membránové glykoproteiny asociované s lyzozomy metabolismus   MeSH
• peptidy chemie   farmakologie   MeSH
• proteiny tepelného šoku HSP70 chemie   MeSH
• receptor 1 spouštějící přirozenou cytotoxicitu metabolismus   MeSH
• receptor 2 spouštějící přirozenou cytotoxicitu metabolismus   MeSH
• receptor 3 spouštějící přirozenou cytotoxicitu metabolismus   MeSH
• receptory IgG metabolismus   MeSH
• receptory KIR2DL2 MeSH
• receptory KIR2DL4 metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakty MeSH

• MeSH
• buňky NK fyziologie   MeSH
• interleukiny analýza   fyziologie   MeSH
• myši MeSH
• placenta imunologie   MeSH
• plod imunologie   MeSH
• těhotenství u zvířat imunologie   MeSH
• Th1 buňky fyziologie   MeSH
• Th2 buňky fyziologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH

• Klíčová slova
• bimekizumab,
• MeSH
• biologická terapie metody   MeSH
• humanizované monoklonální protilátky * farmakologie   škodlivé účinky   terapeutické užití   MeSH
• interleukin-17 antagonisté a inhibitory   MeSH
• lidé středního věku MeSH
• lidé MeSH
• psoriáza * farmakoterapie   patologie   MeSH
• terapie neúspěšná MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

• Publikační typ
• abstrakt z konference MeSH