Natural killer and lymphokine-activated killer cell activities from human marrow precursors. II. The effects of IL-3 and IL-4 Journal Article
| Authors: | Keever, C. A.; Pekle, K.; Gazzola, M. V.; Collins, N. H.; Bourhis, J. H.; Gillio, A. |
| Article Title: | Natural killer and lymphokine-activated killer cell activities from human marrow precursors. II. The effects of IL-3 and IL-4 |
| Abstract: | Both IL-3 and IL-4 have multi-CSF activity on early marrow progenitors. We have examined the effect of IL-3 and IL-4 on the differentiation of NK cells from their marrow-derived precursors and have further examined the interactions of these cytokines with IL-2 and IL-1. We tested marrow which had been depleted of mature cells and of E rosette-positive cells (including NK cells) by treatment with soybean lectin and SRBC (SBA-E-BM). The cytolytic activities of the SBA-E-BM samples were tested in 51Cr-release assays after 7 days of liquid culture. K562 targets were used as a measure of NK activity and NK-resistant Daudi targets were used to measure lymphokine-activated killer (LAK) cell activity. Neither NK nor LAK activity was detectable in marrow cultured in medium without cytokines, or in medium containing IL-3, or IL-4 alone. Both of these cytokines were shown to be inhibitory to the IL-2-induced generation of NK and LAK activity from SBA-E-BM at concentrations as low as 1 U/ml. The inhibitory activity of both IL-3 and IL-4 was found to occur early in the marrow cultures, with little or no inhibitory effects seen if added 48 h after IL-2. IL-3 appeared to be specifically inhibitory to NK cell precursors since addition of IL-3 to cultures of PBMC did not inhibit IL-2-induced lytic activities. In contrast, IL-4 was equally inhibitory to the activation of marrow and peripheral blood NK cells by IL-2. Mixing experiments demonstrated that the reduced lytic activity in IL-3 or IL-4 containing marrow cultures were not due to suppression of the NK effectors, nor could marrow cultured in IL-3 or IL-4 serve as targets for IL-2-activated NK cells. Phenotype analysis of the lymphoid cells in marrow cultures containing IL-2 combined with IL-3 or IL-4 revealed fewer cells expressing Leu-11 (CD16), or Leu-19 (CD56) and fewer CD16,CD56 coexpressing cells compared with marrow cultured in medium containing IL-2 alone. The inhibitory activity of IL-4, but not IL-3, could be partially reversed if IL-1 was added to the cultures, suggesting that IL-1 and IL-4 have opposing activities on NK cell responsiveness to IL-2. These interactions between cytokines might be important in the regulation of NK cell differentiation and on the functional activity of mature NK cells. |
| Keywords: | human cell; phenotype; cells, cultured; interleukin 2; bone marrow; interleukin 4; lymphocyte activation; kinetics; leukocytes, mononuclear; cell culture; hematopoietic stem cells; natural killer cell; killer cells, natural; cytotoxicity, immunologic; rosette formation; interleukin 1alpha; normal human; culture media; interleukin-2; interleukin-1; interleukin-4; interleukin 3; interleukin-3; lectins; dose-response relationship, immunologic; lymphokine activated killer cell; human; priority journal; article; killer cells, lymphokine-activated; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; suppressor factors, immunologic |
| Journal Title: | Journal of Immunology |
| Volume: | 143 |
| Issue: | 10 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 1989-11-15 |
| Start Page: | 3241 |
| End Page: | 3249 |
| Language: | English |
| PUBMED: | 2809200 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 14 April 2020 -- Source: Scopus |
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