CD16 surface molecules regulate the cytolytic function of CD3CD16+ human natural killer cells.
Monoclonal (IgG) antibodies (MAbs) directed to CD16 molecules efficiently induced lysis of the IgG-binding P815 target cells. A similar effect was observed with selected anti-CD2 MAbs. While combinations of 2 appropriate anti-CD2 MAbs were required for induction of T lymphocyte activation, single stimulatory anti-CD2 MAbs were sufficient for inducing cytolytic function in CD3- CD16+ lymphocytes. In order to study possible regulatory mechanisms existing in the process of activation and induction of the cytolytic machinery of CD3- CD16+ effector cells, we utilized the anti-CD16 OKNK MAb. Being of IgM isotype, the OKNK MAb does not allow cross-linking between CD3- D16+ lymphocytes and target cells. Pre-treatment of effector cells with OKNK MAb sharply inhibited the target cell lysis induced by either anti-CD16 (IgG) MAbs or stimulatory anti-CD2 MAb. Moreover, a strong inhibitory activity of PHA-induced target cell lysis and even of "spontaneous" lysis (at high effector:target ratio) was observed. In contrast, in CD3+ CD16+ clones, OKNK MAb selectively inhibited the cell triggering induced by anti-CD16 MAbs (but not by anti-CD3, anti-CD2 MAbs or PHA). Our data indicate that CD16 receptor molecules expressed by CD3- CD16+ lymphocytes down-regulate cell responses to anti-CD2 MAbs or PHA, and then exert a regulatory role in the cytolytic function of these cells.
Moretta
A
A
Istituto di Istologia ed Embriologia Generale, Università di Genova, Italy.
Tambussi
G
G
Ciccone
E
E
Pende
D
D
Melioli
G
G
Moretta
L
L
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D007132:Immunoglobulin Isotypes