CD28-mediated costimulation is necessary for optimal proliferation of murine NK cells.
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.
Nandi
D
D
Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Gross
J A
JA
Allison
J P
JP
D000818:Animals; D018122:B7-1 Antigen / Q000032:analysis; D018106:CD28 Antigens / Q000502:physiology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D007111:Immunity, Cellular; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D018122:B7-1 Antigen; D018106:CD28 Antigens; D007376:Interleukin-2; D008222:Lymphokines; D013755:Tetradecanoylphorbol Acetate