Cytotoxic and proliferative allospecific T-cell clones contain perforin and mediate anti-CD3-induced cytotoxicity.
Some in vitro-generated allospecific T-cell clones can kill target cells bearing specific antigen, whereas others can only proliferate in response to that antigen. The mechanism of target lysis by clones that exhibit antigen-specific cytotoxicity is thought to involve the exocytosis of lytic granules, which contain the pore-forming protein perforin. Here, CD4+, CD8+, and CD4-8- T-cell clones, positive for CD3 and the alpha/beta T-cell receptor, were tested for their ability to lyse the mouse-anti-human CD3 hybridoma OKT3; this hybridoma has been shown to trigger the cytolytic mechanism in cytotoxic T cells regardless of their clonal specificity. We found that all in vitro-generated allospecific T-cell clones can efficiently lyse the OKT3 targets whether or not they can kill alloantigen-bearing lymphoblastoid B-cell line targets. Furthermore, all tested clones contained perforin. The OKT3 hybridoma was not lysed by perforin-negative, CD3+ leukemic T-cell lines or by CD3- NK clones. Thus, the presence of perforin in T-cell clones correlated with their ability to lyse OKT3 targets, but not with their ability to lyse alloantigen-bearing targets. These results demonstrate that T-cell clones that are nonlytic when activated by specific antigen nevertheless contain a complete lytic mechanism and also support the proposed central role in perforin in that mechanism.
Geisberg
M
M
Laboratories of Human Immunogenetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Terry
L A
LA
Flomenberg
N
N
Dupont
B
B
D000818:Animals; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D002999:Clone Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin