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2B4 stimulation of YT cells induces natural killer cell cytolytic function and invasiveness
Author(s) -
Chuang S. S.,
Kim M. H.,
Johnson L. A.,
Albertsson P.,
Kitson R. P.,
Nannmark U.,
Goldfarb R. H.,
Mathew P. A.
Publication year - 2000
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2000.00031.x
Subject(s) - microbiology and biotechnology , cytolysis , biology , interleukin 21 , lymphokine activated killer cell , major histocompatibility complex , monoclonal antibody , interleukin 12 , natural killer cell , cd8 , cytotoxic t cell , janus kinase 3 , natural killer t cell , cd49b , antibody , immunology , antigen , in vitro , biochemistry
Summary 2B4 is a surface molecule found on all human natural killer (NK) cells, a subset of CD8 + T cells, monocytes and basophils. It was originally identified on mouse NK cells and the subset of T cells that mediate non‐major histocompatibility complex (MHC)‐restricted killing. Recently, 9 we have cloned the human homologue of 2B4 (h2B4) and found h2B4 to also mediate non‐MHC‐restricted cytotoxicity. In this study, we examine h2B4 in regulating various functions of NK cells using a human NK cell line YT, with monoclonal antibody (mAb) C1.7, an antibody that specifically recognizes h2B4. Ligation of surface 2B4 with mAb C1.7 increases YT's ability to destroy tumour cells. In the presence of mAb C1.7, the production of interferon‐γ (IFN‐γ) by YT cells is greatly enhanced. Engagement of surface 2B4 by mAb C1.7 downregulates the expression of h2B4 at the cell surface as well as the expression of h2B4 mRNA. Also, signalling through h2B4 causes the increased expression of matrix metalloproteinase‐2, a member of the matrix degrading proteinase family. Thus, in addition to modulating cytolytic function and cytokine production of NK cells, activation through surface 2B4 may play a role in upregulating the machinery for degradation of extracellular matrices to promote invasion of the tumour by NK cells.