MOUSE NK1.1(-CELLS CAN BE GENERATED BY IL-2 EXPOSURE FROM LYMPHOCYTESWHICH EXPRESS AN INTERMEDIATE-LEVEL OF T-CELL RECEPTOR() CYTOTOXIC T)

NK-like T cells which express the NK1.1 molecule and CD3 (or TCR) of i ntermediate level (CD3(int) or TCRint cells) were recently demonstrate d to be present in various immune organs, and to have NK-like cytotoxi c activity against NK target cells. In this study, we investigated whe ther NK1.1(-) T cells could express NK1.1. We found that NK1.1(+) TCRi nt cells were much more abundant in the liver (20%) than in the spleen (2%). When hepatic and splenic mononuclear cells (MNCs) were cultured either in the absence of IL-2 or in the presence of CD3/TCR cross-lin king, the original NK1.1(+) TCRint cells disappeared. However, when th ey were cultured in the presence of a high dose of IL-2 for 4 days, a new type of NK1.1(+) T cell was formed to the extent of approximately 15-20%, and the liver and spleen contained similar percentages of this new type of NK1.1(+) T cells. The phenotypes of the original and the new type of NK1.1(+) T cells were clearly distinct. The freshly obtain ed NK1.1(+) TCRint cells consisted of double-negative (DN) CD4(-)CD8(- ) cells and single-positive (SP) CD4(+) cells, whereas the new type of NK1.1(+) T cells predominantly consisted of DN CD4(-)CD8(-) cells and SP CD8(+) cells and expressed a high level of CD3 (CD3(high) or TCRhi gh cells). When NK1.1(-) cells or IL-2 receptor beta-chain (IL-2R beta )(-) cells were isolated from the liver and spleen, and cultured in th e presence of IL-2 for 4 days, NK1.1(+) T cells were generated from NK 1.1(-) cells, but not from IL-2R beta(-) cells. Our results suggested that the NK1.1(-) cells, but not IL-2R beta(-) cells, contained the pr ecursor of IL-2-stimulated NK1.1(+) TCRhigh cells. When purified NK1.1 (-) IL-2R beta(+) TCRint cells were cultured in the presence of IL-2 f or 4 days, approximately 10% of the cells became NK1.1(+) TCRhigh cell s. Approximately 60% of the purified NK1.1(+) TCRint cells lost NK1.1 expression. The IL-2-stimulated NK1.1(+) TCRhigh cells that had arisen from NK1.1(-) TCRint cells exerted an NK cell-like cytotoxic activity similar to that of the original NK1.1(+) T cells. Thus, NK1.1- TCRint cells could express NK1.1 and exert NK-like cytotoxic activity regard less of their origin. It appears that NK1.1(+) TCRhigh cells can only be induced through an IL-2-stimulation pathway but not via CD3/TCR cro ss-linking. (C) 1998 Elsevier Science B.V. All rights reserved.