"Anomalous" Thy-1+ killer cells in allogeneic and F1-anti-parental mixed leukocyte culture. Relation to natural killer cells and allospecific cytotoxic T lymphocytes.

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Abstract
Anomalous killer [AK] cells are Thy-1+ blasts that are cytolytic to the natural killer (NK)-sensitive [mouse] lymphoma YAC-1, and they can be detected early (day 3-4) in the period preceeding the allospecific cytotoxic T lymphocyte (CTL) response in (CBA .times. A) F1 .fwdarw. C57B1 mixed leukocyte culture (MLC). The origin and nature of AK were investigated, with special emphasis on its relation to NK- and allospecific CTL-activity. AK was distinct from the previously described NKc-cells induced by cultivation in fetal calf serum (FCS)-supplemented medium when these 2 reactivities were examined in parallel. AK was detected in either FCS- or normal mouse serum (NMS)-supplemented allogeneic MLC, indicating that the response was not dependent on mitogenic or antigenic properties of heterologous serum. In addition to several H-2-incompatible combinations, AK was also observed in an Mls-incompatible (but H-2 compatible) and 2 F1-antiparental MLC responder/stimulator combinations. AK cells showed a similar selectivity pattern to NK cells, as demonstrated in cold target inhibition and direct cytotoxicity assays using variant or interferon-modulated YAC-1 cells with low expression of NK target structures. The AK-cells were NK-1.2-/weak. Thy-1.2+, although they seem to be derived from nonadherent radiosensitive cells which are closely related, if not identical, to NK-cells (NK-1.2+. Thy-1.2-/weak), as they could not be readily induced in responder populations with low NK-activity, but normal allospecific CTL potential. An in vivo thymectomy protocol or treatment of normal spleen cells with monoclonal anti-Thy-1.2 + C reduced the allospecific CTL response drastically but did not affect the AK response. AK cells were not observed when MLC were prepared with responder as well as stimulator cells devoid of mature T cells. In such a combination, the AK response was partially restored by the addition of irradiated +/nu (but not nu/nu) responder cells to the cultures. When normal (non-nude) spleen cells were used as responders, induction of AK did not require the presence of T cells in the stimulator population; the removal of adherent and phagocytic cells from stimulators abrogated the response. AK apparently represents activation, blast transformation and surface marker modulation of NK cells induced by alloantigen-stimulated T cells, resulting in Thy-1+ cytolytic cells with similar properties to those described for NK lines. Although AK cells may be regarded as a more T cell-like NK phenotype, their induction is neither necessary nor sufficient for generation of specific CTL in MLC.