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Interleukin-15-induced maturation of human natural killer cells from early thymic precursors: selective expression of CD94/NKG2-A as the only HLA class I-specific inhibitory receptor.
Eur J Immunol. 1997 Jun; 27(6):1374-80.EJ

Abstract

Immature postnatal thymocytes were shown to contain precursors which, under suitable culture conditions, give rise to phenotypically and functionally mature natural killer (NK) cells. Here, we analyzed the effect of different cytokines for their ability to induce the expression of HLA class I-specific inhibitory receptor(s) during the process of NK cell development from immature thymocytes. From thymocyte cell suspensions depleted of CD2+, CD3+, CD4+, CD8+, CD56+, and CD16+ cells, we further removed cells expressing HLA class I-specific inhibitory receptors including CD94/NKG2-A, p58.1, and p58.2 by immunomagnetic bead separation. The resulting cells did not contain any of the above NK receptors as determined by immunofluorescence and flow cytometric analysis, as well as by reverse transcriptase polymerase chain reaction (RT-PCR) amplification using appropriate sets of primers. Although different cytokines have been used, including interleukin (IL)-7, stem cell factor (SCF), IL-2, and IL-15, only IL-2 or IL-15 induced cell proliferation when used alone. Moreover, maturation towards CD3- CD56+ cells displaying cytolytic activity against the HLA class I- targets K562 or 221 was detectable in cultures containing IL-15 used alone or in combination with IL-7 or SCF. On the other hand, these CD3- CD56+ cell populations did not lyse HLA class I+ target cells, including autologous PHA blasts. Analysis of the expression of the various HLA class I-specific inhibitory NK receptors revealed the presence of high proportions of CD94/ NKG2-A+ cells, while the NK receptors belonging to the Ig superfamily were undetectable both by immunofluorescence and by RT-PCR analysis. The expression of CD94/NKG2-A appeared to be responsible for the inability of cells to lyse HLA class I+ target cells. Thus, addition of anti-CD94 monoclonal antibodies of IgM isotype resulted in lysis of autologous target cells. The use of 221 cells transfected with different HLA class I alleles as target cells confirmed the broad class I specificity of CD94/NKG2-A receptor. Our experiments indicate that IL-15 provides an appropriate stimulus to the expression of CD94/NKG2-A, but not of other class I-specific NK receptors in the process of maturation of NK cells from thymocyte precursors.

Authors+Show Affiliations

Dipartimento di Oncologia Clinica e Sperimentale, Università di Genova, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9209487

Citation

Mingari, M C., et al. "Interleukin-15-induced Maturation of Human Natural Killer Cells From Early Thymic Precursors: Selective Expression of CD94/NKG2-A as the Only HLA Class I-specific Inhibitory Receptor." European Journal of Immunology, vol. 27, no. 6, 1997, pp. 1374-80.
Mingari MC, Vitale C, Cantoni C, et al. Interleukin-15-induced maturation of human natural killer cells from early thymic precursors: selective expression of CD94/NKG2-A as the only HLA class I-specific inhibitory receptor. Eur J Immunol. 1997;27(6):1374-80.
Mingari, M. C., Vitale, C., Cantoni, C., Bellomo, R., Ponte, M., Schiavetti, F., Bertone, S., Moretta, A., & Moretta, L. (1997). Interleukin-15-induced maturation of human natural killer cells from early thymic precursors: selective expression of CD94/NKG2-A as the only HLA class I-specific inhibitory receptor. European Journal of Immunology, 27(6), 1374-80.
Mingari MC, et al. Interleukin-15-induced Maturation of Human Natural Killer Cells From Early Thymic Precursors: Selective Expression of CD94/NKG2-A as the Only HLA Class I-specific Inhibitory Receptor. Eur J Immunol. 1997;27(6):1374-80. PubMed PMID: 9209487.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interleukin-15-induced maturation of human natural killer cells from early thymic precursors: selective expression of CD94/NKG2-A as the only HLA class I-specific inhibitory receptor. AU - Mingari,M C, AU - Vitale,C, AU - Cantoni,C, AU - Bellomo,R, AU - Ponte,M, AU - Schiavetti,F, AU - Bertone,S, AU - Moretta,A, AU - Moretta,L, PY - 1997/6/1/pubmed PY - 1997/6/1/medline PY - 1997/6/1/entrez SP - 1374 EP - 80 JF - European journal of immunology JO - Eur J Immunol VL - 27 IS - 6 N2 - Immature postnatal thymocytes were shown to contain precursors which, under suitable culture conditions, give rise to phenotypically and functionally mature natural killer (NK) cells. Here, we analyzed the effect of different cytokines for their ability to induce the expression of HLA class I-specific inhibitory receptor(s) during the process of NK cell development from immature thymocytes. From thymocyte cell suspensions depleted of CD2+, CD3+, CD4+, CD8+, CD56+, and CD16+ cells, we further removed cells expressing HLA class I-specific inhibitory receptors including CD94/NKG2-A, p58.1, and p58.2 by immunomagnetic bead separation. The resulting cells did not contain any of the above NK receptors as determined by immunofluorescence and flow cytometric analysis, as well as by reverse transcriptase polymerase chain reaction (RT-PCR) amplification using appropriate sets of primers. Although different cytokines have been used, including interleukin (IL)-7, stem cell factor (SCF), IL-2, and IL-15, only IL-2 or IL-15 induced cell proliferation when used alone. Moreover, maturation towards CD3- CD56+ cells displaying cytolytic activity against the HLA class I- targets K562 or 221 was detectable in cultures containing IL-15 used alone or in combination with IL-7 or SCF. On the other hand, these CD3- CD56+ cell populations did not lyse HLA class I+ target cells, including autologous PHA blasts. Analysis of the expression of the various HLA class I-specific inhibitory NK receptors revealed the presence of high proportions of CD94/ NKG2-A+ cells, while the NK receptors belonging to the Ig superfamily were undetectable both by immunofluorescence and by RT-PCR analysis. The expression of CD94/NKG2-A appeared to be responsible for the inability of cells to lyse HLA class I+ target cells. Thus, addition of anti-CD94 monoclonal antibodies of IgM isotype resulted in lysis of autologous target cells. The use of 221 cells transfected with different HLA class I alleles as target cells confirmed the broad class I specificity of CD94/NKG2-A receptor. Our experiments indicate that IL-15 provides an appropriate stimulus to the expression of CD94/NKG2-A, but not of other class I-specific NK receptors in the process of maturation of NK cells from thymocyte precursors. SN - 0014-2980 UR - https://www.unboundmedicine.com/medline/citation/9209487/Interleukin_15_induced_maturation_of_human_natural_killer_cells_from_early_thymic_precursors:_selective_expression_of_CD94/NKG2_A_as_the_only_HLA_class_I_specific_inhibitory_receptor_ L2 - https://doi.org/10.1002/eji.1830270612 DB - PRIME DP - Unbound Medicine ER -