Heterogeneous binding and killing behaviour of human gamma/delta-TCR+ lymphokine-activated killer cells against K562 and Daudi cells.
Effector-target conjugates, formed by coincubation of lymphokine-activated killer (LAK) cells with either K562 or Daudi cells, were separated from single cells by Percoll sedimentation. The occurrence of various CD molecules (CD3, CD56, CD57, CD16, gamma/delta-TCR) was compared in both fractions. Only LAK cells expressing the gamma/delta T cell receptor (TCR) were found in a significantly increased percentage in fractions containing conjugates indicating that gamma/delta-TCR+ LAK cells were preferably bound to target cells at the time of separation. In order to determine whether gamma/delta-TCR+ LAK cells also show a preferred killing activity against the targets, cultures enriched with or depleted of gamma/delta-TCR+ cells were established. Against K562 cells, gamma/delta-TCR(+)-enriched cultures showed a greatly reduced killing activity compared to LAK bulk cultures or cultures depleted of gamma/delta-TCR+ cells. Using Daudi cells as targets the enriched fraction revealed a slightly increased killing activity compared to bulk cultures or depleted fractions. Preincubation of gamma/delta-TCR+ LAK cells with anti-gamma/delta or anti-CD3 mAb resulted in a distinct increase of the killing activity against K562 cells, but in only a slightly enhanced activity against Daudi cells. It is postulated that gamma/delta-TCR+ LAK cells use the same adhesion mechanism for both targets but that only Daudi cells express a specific ligand for the gamma/delta-TCR. Occupation of the gamma/delta-TCR/CD3 complex by mAb, however, seems to substitute for the absent epitope on K562 cells by eliciting stimulatory signals in gamma/delta-TCR+LAK cells which, in combination with the binding stimulus, trigger cytolytic activity.
Vollenweider
I
I
Institute of Anatomy, University of Zürich-Irchel, Switzerland.
Vrbka
E
E
Fierz
W
W
Groscurth
P
P
D002448:Cell Adhesion; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007111:Immunity, Cellular; D016130:Immunophenotyping; D066298:In Vitro Techniques; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014407:Tumor Cells, Cultured
D016692:Receptors, Antigen, T-Cell, gamma-delta