Perforin-dependent killing of tumor cells by Vgamma1Vdelta1-bearing T-cells.
The T-cell subset expressing Vdelta2 paired primarily with Vgamma2 comprises a majority of gammadelta T-cells in human adult peripheral blood and expands significantly during a variety of infectious diseases. In contrast, the other subset of gammadelta T-cells that express Vdelta1 is rare among circulating T-cells and its function is poorly understood. Here, we show that a Vgamma1Vdelta1(+) T-cell line, 3-D, established from human peripheral blood by immortalization with Herpesvirus saimiri was able to specifically recognize tumor cells, such as K562 cells, and release cytotoxic granules containing perforin for target cell killing. Some tumor cells, including Daudi cells that are known to be susceptible to killing by Vdelta2(+) T-cells, were resistant to 3-D killing, implicating distinct pathways for tumor cell control by Vdelta1(+) and Vdelta2(+) T-cells. The 3-D T-cell receptor (TCR):CD3 complex reconstituted in TCR-deficient Jurkat cells was capable of transmitting signals, evidenced by activation of the interleukin 2 (IL-2) gene following ligation with anti-CD3 antibody, yet the TCR-reconstituted cells failed to produce IL-2 in response to the target cells. Thus, these results raise the possibility that some Vgamma1Vdelta1(+) T-cells could potentially be stimulated and lyse tumor cells via ligation of TCR/CD3-unassociated molecules.
Narazaki
Hidehiko
H
Department of Microbiology and Immunology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
Watari
Eiji
E
Shimizu
Masumi
M
Owaki
Atsuko
A
Das
Hiranmoy
H
Fukunaga
Yoshitaka
Y
Takahashi
Hidemi
H
Sugita
Masahiko
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017252:CD3 Complex / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D022801:Complementarity Determining Regions / Q000235:genetics; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D006567:Herpesvirus 2, Saimiriine; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism; D007938:Leukemia / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014407:Tumor Cells, Cultured
D017252:CD3 Complex; D015704:CD4 Antigens; D022801:Complementarity Determining Regions; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054353:Perforin