CD28-mediated costimulation is necessary for optimal proliferation of murine NK cells.

• DOI: 10.4049/jimmunol.152.7.3361
• Publication Date: 2022-12-31T11:17:06Z
• Authors: D Nandi; J A Gross; J P Allison
• Keywords: Cytotoxicity, Immunologic; 0301 basic medicine; Immunity, Cellular; Lymphokines; Mice, SCID; Lymphocyte Activation; Killer Cells, Natural; Mice, Inbred C57BL; Mice; 03 medical and health sciences; CD28 Antigens; B7-1 Antigen; Animals; Interleukin-2; Tetradecanoylphorbol Acetate; Female

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.