Defective Mononuclear Cell Antibody-Dependent Cellular Cytotoxicity (ADCC) in Patients with Leukocyte Adhesion Deficiency Emphasizing on Different CD11/CD18 Requirement of FcγRI versus FcγRII in ADCC

The defective antibody-dependent cellular cytotoxicity (ADCC) of mononuclear cells (MNC) from patients with leukocyte adhesion deficiency (LAD), β2integrins (CD11a-c/CD18) deficiency was shown. LAD patients completely failed to generate MNC-ADCC against sheep red blood cells (SRBC) sensitized with murine (m) IgG2b, but had diminished but significant cytolysis against mIgG2a-SRBC, suggesting that the CD11/CD18 requirement of FcγRI is different from that of FcγRII in MNC-ADCC. Blocking experiments with monoclonal antibodies (mAb) against individual subunits of CD11/CD18 revealed that anti-CD18 mAb almost completely inhibited mlgG2b-mediated ADCC by normal monocytes, but only partially inhibited mlgG2a-mediated ADCC. These data may confirm the evidence that FcγRII-mediated ADCC absolutely requires CD11/CD18 but FcγRI-mediated ADCC does not. Among subunits of CD11/CD18, CD18 appeared to be most involved in lysis of sensitized SRBC.