CD28 is not directly involved in the response of human CD3- CD56+ natural killer cells to lipopolysaccharide: a role for T cells.
We have previously shown that human CD3- CD56+ and CD3+ CD56+ cells from some individuals mount vigorous proliferative responses to lipopolysaccharide. Such responses have been blocked by the presence of cytotoxic T-lymphocyte antigen-4 immunoglobulin fusion protein in the cultures, implicating a role for B7-mediated costimulation. Here we confirm this inhibition of natural killer (NK) expansion using antibodies against B7-1 and B7-2. We were unable to specifically detect CD28 on the surface of resting or stimulated human peripheral blood NK cells, however, in either lipopolysaccharide-responsive or non-responsive individuals, using a panel of four different anti-CD28 monoclonal antibodies. T-cell depletion from peripheral blood mononuclear cell cultures resulted in a reduction in the induction of CD25 on activated CD3- CD56hi cells and in the expansion and proliferation of CD3- CD56+ NK cells. Furthermore, reconstitution experiments using peripheral blood dendritic cells and purified NK cells demonstrated that NK expansion could only be achieved in the presence of purified T cells.
Goodier
M R
MR
Department of Immunology, Imperial College London, Chelsea and Westminster Hospital, London, UK. m.goodier@imperial.ac.uk
Londei
M
M
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000276:immunology*; D017252:CD3 Complex / Q000097:blood; D019002:CD56 Antigen / Q000097:blood*; D002450:Cell Communication / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D017252:CD3 Complex; D019002:CD56 Antigen; C497964:CD86 protein, human; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D015375:Receptors, Interleukin-2