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Artificial Antigen Presenting Cell (aAPC) Mediated Activation and Expansion of Natural Killer T Cells
Published on: December 29, 2012
CD28-mediated costimulation is necessary for optimal proliferation of murine NK cells
D Nandi1, J A Gross, J P Allison
1Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Insights
Natural killer (NK) cells require CD28 costimulatory signals for optimal proliferation and cytokine production, but not for cytotoxicity. This finding highlights the functional role of CD28 in NK cell responses.
Area of Science:
- Immunology
- Cell Biology
Background:
- CD28 is a critical costimulatory molecule for T cell activation.
- Natural killer (NK) cells are immune cells with cytotoxic and cytokine-producing functions.
Purpose of the Study:
- To investigate the expression and function of CD28 on murine NK cells.
- To determine the role of CD28-mediated costimulation in NK cell proliferation, cytokine production, and cytotoxicity.
Main Methods:
- Flow cytometry to detect CD28 expression on NK cells.
- In vitro stimulation assays using IL-2, PMA, anti-CD28, and L-B7+ cells.
- Measurement of NK cell proliferation, cytokine (IFN-gamma, TNF) production, and cytotoxicity.
Main Results:
- NK-1.1+ cells and IL-2-activated NK cells express CD28 at lower levels than T cells.
- CD28 costimulation, along with IL-2 and PMA, significantly enhanced NK cell proliferation.
- CD28 signaling boosted IFN-gamma and TNF production by IL-2-activated NK cells.
- CD28 signaling did not affect NK-mediated cytotoxicity.
Conclusions:
- The CD28 costimulatory pathway is functional in murine NK cells.
- CD28 plays a crucial role in regulating NK cell proliferation and cytokine production.
- CD28 signaling does not appear to influence NK cell-mediated cytotoxicity.
Abstract:
CD28, a cell surface molecule expressed on all murine T cells, plays a critical role in T cell activation. We show here that NK-1.1+ cells, a subpopulation of SCID splenocytes, and IL-2-activated NK cells express CD28, although at lower levels than alpha beta T cells. Optimal proliferation of highly purified asialo GM1+ NK cells from the SCID spleen was observed in response to stimulation with IL-2 and PMA, together with anti-CD28 or L-B7+ cells. Thus, in addition to IL-2, murine NK cells require CD28-mediated costimulatory signals for optimal proliferation. IL-2-activated NK cells produced enhanced levels of IFN-gamma and TNF in response to stimulation with anti-CD28 and PMA. On the other hand, we were unable to demonstrate that CD28 signaling had any effect on NK-mediated cytotoxicity. We conclude that the CD28 costimulatory pathway is functional in NK cells and plays an important role in their proliferation and cytokine production.
