Natural killer (NK) cells (poly I:C induced, x-ray resistant, nonadherent, Thy-1-, Ly-1.1-, Ly-2.1-, anti-asialo GM1-positive, and cytotoxic for YAC-1) suppressed T lymphocyte proliferation in mixed lymphocyte reaction (MLR) and autologous MLR cultures. Dendritic cells (DC) were required for proliferation of lymphocytes in both responses. The question whether lymphocytes or DC were the targets for NK cells was resolved by taking advantage of the fact that NK cells, but not DC, lose activity after 24 h in culture. Three findings indicate that DC, not lymphocytes, are targets for NK cells. First, responses suppressed by NK cells were fully restored by adding small numbers of DC to cultures 24 h after NK cells had been added. Second, DC incubated alone with NK cells and antigen for 24 h did not stimulate proliferation of lymphocytes. Third, lymphocytes incubated alone with NK cells for 24 h proliferated normally when DC were added. Additional experiments showed that DC became targets only after interaction with antigen. Thus, we suggest that NK cells may regulate lymphocyte proliferation by monitoring antigen presentation by DC.

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