Activation of NK Cells in Mixed Cultures of Wharton’s Jelly Mesenchymal Stromal Cells and Peripheral Blood Lymphocytes
Mesenchymal stromal cells possess immunosuppressive properties that might be used for the therapy of inflammatory diseases of various geneses. The effects of mesenchymal stromal cells depend on their lifetime in the recipient tissues. During heterologous transplantation, mesenchymal stromal cells are eliminated by NK cells. We studied NK cell formation in mixed cultures of Wharton’s jelly mesenchymal stromal cells and peripheral blood lymphocytes from an autologous donor. Lymphocytes were activated by a mitogen or IL-2. The lifetime of mesenchymal stromal cells was estimated by MTT test. Cytotoxic activity and phenotype of NK cells were evaluated by flow cytometry. It was found that activation of NK cells depended on IL-2 and was registered on day 2 of incubation with IL-2. In cultures with mitogen-activated lymphocytes, cytotoxicity was observed after 5-6 days. Cytotoxicity of NK correlated with significant decrease in CD16+ and increase in CD56+ NK and with reduction of mesenchymal stromal cell viability. Thus, the main mechanism of elimination of mesenchymal stromal cells is cytotoxicity of NK cells that depended on IL-2 production.
Key Wordsmesenchymal stromal cells lymphocyte activation natural killers
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- 3.DelaRosa O, Sánchez-Correa B, Morgado S, Ramírez C, del Río B, Menta R, Lombardo E, Tarazona R, Casado JG. Human adipose-derived stem cells impair natural killer cell function and exhibit low susceptibility to natural killer-mediated lysis. Stem Cells Dev. 2012;21(8):1333-1343.CrossRefPubMedGoogle Scholar
- 8.Mavilio D, Lombardo G, Benjamin J, Kim D, Follman D, Marcenaro E, O’Shea M.A, Kinter A, Kovacs C, Moretta A, Fauci AS. Characterization of CD56—/CD16+ natural killer (NK) cells: a highly dysfunctional NK subset expanded in HIV-infected viremic individuals. Proc. Natl Acad. Sci. USA. 2005;102(8):2886-2891.Google Scholar
- 9.Tseng HC, Arasteh A, Paranjpe A, Teruel A, Yang W, Behel A, Alva JA, Walter G, Head C, Ishikawa TO, Herschman HR, Cacalano N, Pyle AD, Park NH, Jewett A. Increased lysis of stem cells but not their differentiated cells by natural killer cells; de-differentiation or reprogramming activates NK cells. PLoS One. 2010;5(7):e11590. doi: https://doi.org/10.1371/journal.pone.0011590.CrossRefPubMedPubMedCentralGoogle Scholar
- 10.Wang W, Erbe AK, Alderson KA, Phillips E, Gallenberger M, Gan J, Campana D, Hank JA, Sondel PM. Human NK cells maintain licensing status and are subject to killer immunoglobulin-like receptor (KIR) and KIR-ligand inhibition following ex vivo expansion. Cancer Immunol. Immunother. 2016;65(9):1047-1059.CrossRefPubMedPubMedCentralGoogle Scholar