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 TcR/CD3-controlled alternative activation routes such as the CD2 activation pathway.
Van Seventer
G A
GA
Central Laboratory of the Netherlands, Red Cross Blood Transfusion Service, Amsterdam.
Van Lier
R A
RA
Kuijpers
K C
KC
Spits
H
H
Melief
C J
CJ
D000911:Antibodies, Monoclonal / Q000276:immunology; D000937:Antigen-Antibody Reactions; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D018801:CD2 Antigens; D017252:CD3 Complex; D016827:CD8 Antigens; D002478:Cells, Cultured; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D006681:HLA-D Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D016827:CD8 Antigens; D006681:HLA-D Antigens; D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic