A revertant TCR gamma delta + cell clone which has lost MHC nonrestricted cytotoxic activity but retains redirected killing upon stimulation of the CD3 receptor.
A variant nonkiller (K-) T-cell clone derived from the MHC nonrestricted killer (K+) cell line TALL-103/2 (CD3/TCR gamma delta +) was studied to determine whether its lytic defects were at the tumor-binding or post-binding level. The two TALL-103/2 clones were found to display similar mRNA expression of TCR/CD3 complex epsilon, zeta, gamma, and delta chains, and the same mRNA and protein levels of SRC-like protein tyrosine kinase and kinase activity. However, the K- cells express much less surface CD45 RA and contain smaller intracytoplasmatic cytotoxic granules with a lower expression of the TIA-1 protein. Although the K- cells do not undergo granule exocytosis upon contact with a susceptible (K562) target, they can be triggered to degranulate and display redirected killing by activation of the CD3 receptor. Moreover, OKT3 induces PPI turnover and Ca2+ mobilization in both the K+ and K- cells, whereas K562 cells induces PPI turnover only in the K+ clone. The overall data indicate that, although the K- cells have significant post-binding defects that prevent them from killing MHC nonrestricted targets, they can fully utilize their lytic machinery upon specific activation of the CD3 pathway.
Visonneau
S
S
Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Cesano
A
A
Santoli
D
D
D000818:Animals; D017252:CD3 Complex / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D003594:Cytoplasmic Granules; D003602:Cytotoxicity, Immunologic; D053804:Granzymes; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008811:Mice, Inbred DBA; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D012697:Serine Endopeptidases / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D017252:CD3 Complex; D018129:Phosphatidylinositol Phosphates; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human; D002118:Calcium