Studies on Cytotoxicity Generated in Human Mixed Lymphocyte Cultures

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Abstract
In addition to the allospecific killing detected against Con A blasts, 5-day MLC (X vs Ym) cells have a cytotoxic effect against K562 and the autologous (X) lymphoblastoid cell line (auto LCL). This effect is designated as anomalous killing or, AK. Both the AK and allospecific killing could be generated with purified E-rosetting cells, indicating that the effectors were T cells. However, they appeared to belong to different populations, based on three criteria: 1) Upon secondary challenge with the original stimulating cells, allospecific killing displayed a classical memory response. In contrast, peak AK activity against both K562 and the auto LCL was weaker in the secondary, compared to the primary culture. 2) The AK and allo targets did not cross-compete in cold target inhibition tests. 3) AK and allocytotoxicity distributed differently after fractionation of the MLC cells on immobilized immune complexes (IC plates). AK effectors may be similar to natural killer (NK) cells, as they preferentially kill K562 and other NK-sensitive targets. However, the anti-K562 effect was not entirely the result of persisting NK cells because the activity could be generated from Fc receptor-negative, NK-negative precursors. Furthermore, in contrast to NK cells, the AK effector cells could not be efficiently depleted by attachment to IC plates, suggesting that NK and AK differ with respect to expression of Fc receptors. The relationship between these two effects, as well as the conditions involved in activating AK, requires further clarification.

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