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.
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 micrograms/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.
Somersalo
K
K
Department of Pathology, University of Helsinki, Finland.
Carpén
O
O
Saksela
E
E
D002448:Cell Adhesion; D002634:Chemotaxis, Leukocyte; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000378:metabolism; D017469:Receptors, Fibronectin / Q000378:metabolism*; D016029:Receptors, Very Late Antigen / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*
D016209:Interleukin-8; D012333:RNA, Messenger; D017469:Receptors, Fibronectin; D016029:Receptors, Very Late Antigen