CYTOTOXIC ACTIVITY AGAINST TUMOR-CELLS MEDIATED BY INTERMEDIATE TCR CELLS IN THE LIVER AND SPLEEN

Morphological and phenotypic characterization in previous studies has indicated that intermediate (int) T-cell receptor (TCR) cells or T nat ural killer (T-NK) cells may stand at an intermediate position between NK cells and high TCR cells of thymic origin in phylogenetic developm ent. In this study, a functional study on cytotoxic activity against v arious tumour targets was performed in each purified subset. When a ne gative selection method entailing in vivo injection of anti-asialo GM( 1) antibody or anti-interleukin (IL)-2R beta monoclonal antibody (mAb) was applied, IL-2R beta(+) CD3(-) NK cells were found to have the hig hest NK activity while IL-2R beta(+) int CD3 (or TCR) cells had a lowe r level of the NK activity. High CD3 cells (freshly isolated) did not have any such activity. Sorting experiments further revealed that the NK function mediated by int CD3 cells was augmented when they were exp osed to anti-CD3 mAb, anti-TCR alpha beta, or anti-TCR gamma delta mAb . This phenomenon was not observed in NK cells and high CD3 cells. Mor e importantly, when anti-CD3 mAb (or anti-TCR mAb) was added to the as say culture, int CD3 cells became cytotoxic against even NK-resistant tumour (Fc gamma R(-), Fas(+)) targets. Liver mononuclear cells or int CD3 cells exposed to anti-CD3 mAb for 6 hr showed an elevated level o f perforin in their cytoplasms. The present results suggest that int C D3 cells are usually noncytotoxic against Various tumours but become f unctional after being stimulated via the TCR-CD3 complex.