Stimulated natural killer cells secrete factors with chemotactic activity, including NAP‐1/IL‐8, which supports VLA‐4‐ and VLA‐5‐mediated migration of T lymphocytes

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Abstract
In vivo, natural killer (NK) cells dominate among the early invading cells in allografts and virus‐infected tissues, and they are followed later by an influx of T cells. The same sequence of events was seen in our modified Boyden chamber assay. The migration of both CD3+/CD4+ and CD3+/CD8+ cells through fibronectin‐coated filters increased after co‐culture with NK cells. The migratory response to a soluble factor from NK cells supernatants was predominantly chemotactic rather than chemokinetic. Endogenous NK cells, purified in the presence of human serum albumin, did not induce T cell chemotaxis, but NK cells which were purified in the presence of 10% fetal calf serum (FCS), or which were activated in the absence of FCS with 10−4 M histamine, with 300 IU/ml interleukin (IL)‐2, or with a combination of 10 IU/ml IL‐2 and 10 μg/ml CD16 monoclonal antibody increased T cell migration by 30–70%. Both the random and chemotactic migration were dependent on fibronectin receptors VLA‐4 and VLA‐5 on T cells. About 60% of the chemotactic was neutralized by NAP‐1/IL‐8 polyclonal antibody. Northern blot analysis revealed IL‐8 mRNA expression in highly purified, stimulated NK cells; dimeric IL‐8 protein secreted by NK cells was detected by immunoblotting, and, in immunofluorescence staining IL‐8 was visualized in NK cells. These observations suggest that NK cells, early invaders in the foci of injury, participate in the initiation of a specific immune response by facilitating T cell recruitment.

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