Regulatory role of the CD8 antigen in both CD3 and CD2 monoclonal antibody -induced nonspecific cytotoxicity of class I-and class II-allospecific cytotoxic T cell clones*
We investigated the function of the CD8 moiety in antigen-specific and alternative activation of HLA class I-and HLA class II-allospecific CD8' cytotoxic T lymphocyte (CTL) clones, Monoclonal antibodies (mAb) directed against the CD8 structure were only found to inhibit antigen-specific cytotoxicity of class I-allospecific CD8' CTL clones and not of a class II-allospecific CD8' CTL clone. However, cytotoxicity induced by CD3 mAb (used at suboptimal concentrations) or CD2 mAb in both types of CTL clone was blocked by CD8 mAb. The class II-allospecific CD8+ CTL clone was uniformly more difficult to inhibit than the class I-allospecific CD8' CTL clones and, moreover, also easier to induce to exert nonspecific cytotoxicity by CD2 mAb and CD3 mAb. The absence of CD8 mAb blocking of antigen-specific cytotoxicity of the class II-specific CD8' CTL clone is, therefore, assumed to result from too strong a triggering signal to be overcome by the down-regulatory signal of the CD8 antigen. These combined findings suggest a down-regulatory function of CD8 not only in T cell receptor (TcR)/CD3 activation, but also in TcRKD3-controlled alternative activation routes such as the CD2 activation pathway.