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Phenotypic and functional characterization of long-lived NK cell lines of different maturational status obtained from mouse fetal liver

Lookup NU author(s): Dr Jennifer Toomey, Professor Colin Brooks

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Abstract

Culture of day 14 mouse fetal liver (FL) cells in high dose IL-2, together with appropriate combinations of IL-4 and PMA, resulted in the generation of cell lines, termed FL-A lines, that were phenotypically and functionally indistinguishable from cultured adult splenic NK cell populations with the single important exception that no Ly49-expressing cells were present. By contrast, when FL cells were cultured in low-dose IL-2 alone, a second population of slow-growing NK-like cells, termed FL-B cells, emerged. These cells expressed the NK markers asialoGM1, 10A7, 2B4, and Fc gamma RII/III but differed from FL-A and splenic NK cells in expressing IL-2R alpha and stem cell factor receptor (SCFR) but no B220. Most lines derived in this manner had minimal or no cytolytic activity and only very low levels of NK1.1. However, they could secrete substantial quantities of several lymphokines including IL-3, granulocyte-macrophage (CM)-CSF, TNF-alpha; and, most surprisingly, IL-2. A minority of FL-B lines, typified by line 903, displayed marked cytolytic activity, moderate levels of NK1.1, reduced production of IL-2, and the capacity for accelerated growth in high-dose IL-2. FL-B lines generally expressed mRNA for CD3 gamma but not for other CD3 chains, whereas FL-A and fetal thymic (FT) NK lines often expressed mRNA for all four CD3 chains. Despite many similarities to pro-T cells, FL-B cells showed no capacity to differentiate into mature T cells. Taken together, our results suggest that NK lines of different maturity can be obtained from fetal liver, with FL-B lines being the most immature, FL-A lines the most mature, and lines such as FL-B 903 representing an intermediate state of differentiation.


Publication metadata

Author(s): Manoussaka M, Georgiou A, Rossiter B, Shrestha S, Toomey JA, Sivakumar PV, Bennett M, Kumar V, Brooks CG

Publication type: Article

Publication status: Published

Journal: Journal of Immunology

Year: 1997

Volume: 158

Issue: 1

Pages: 112-119

Print publication date: 01/01/1997

Acceptance date: 14/10/1996

ISSN (print): 0022-1767

ISSN (electronic): 1550-6606

Publisher: American Association of Immunologists

URL: http://www.jimmunol.org/content/158/1/112.abstract


Funding

Funder referenceFunder name
AI 25401NIAID NIH HHS
AI 38938NIAID NIH HHS
CA 36921NCI NIH HHS

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