A revertant TCR gamma delta + cell clone which has lost MHC nonrestricted cytotoxic activity but retains redirected killing upon stimulation of the CD3 receptor

Cell Immunol. 1995 Oct 15;165(2):252-65. doi: 10.1006/cimm.1995.1212.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD3 Complex / physiology*
  • Calcium / metabolism
  • Cytoplasmic Granules
  • Cytotoxicity, Immunologic*
  • Granzymes
  • Humans
  • Interferon-gamma / biosynthesis
  • Mice
  • Mice, Inbred DBA
  • Phosphatidylinositol Phosphates / metabolism
  • Protein-Tyrosine Kinases / metabolism
  • RNA, Messenger / analysis
  • Receptors, Antigen, T-Cell, gamma-delta / analysis*
  • Serine Endopeptidases / metabolism
  • T-Lymphocytes / immunology*
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • CD3 Complex
  • Phosphatidylinositol Phosphates
  • RNA, Messenger
  • Receptors, Antigen, T-Cell, gamma-delta
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Protein-Tyrosine Kinases
  • Granzymes
  • Serine Endopeptidases
  • GZMA protein, human
  • Calcium