NK cell trafficking and cytokine expression in splenic compartments after IFN induction and viral infection.
Studies were undertaken to characterize mechanisms for NK cell cytokine delivery in vivo. Conditions of systemic IFN-beta expression elicited by polyinosinic-polycytidylic acid (poly(I:C)) treatment or IFN-alpha beta production during lymphocytic choriomeningitis virus or murine cytomegalovirus infections resulted in profound splenic histologic changes, with relocalization of nucleated cells from red to white pulp regions. Cell-trafficking experiments, with fluorescently labeled populations, showed that poly(I:C) induced T/B cell-dependent leukocyte migration into white pulp regions. Splenic leukocytes prepared from severe combined immunodeficient (SCID) and bone marrow cells prepared from SCID or normal C57BL/6 mice revealed a unique poly(I:C)-induced accumulation of non-T/non-B cells along splenic red and white pulp region borders characteristic of marginal zones. Lymphocytic choriomeningitis virus and murine cytomegalovirus infections also induced this trafficking pattern. Ab treatments of normal and SCID cell donor mice to eliminate specific cell subsets demonstrated that the unique migration of non-T/non-B cells was dependent upon cells with the NK phenotype, NK1.1+ AGM1+F4/80-. In situ hybridization showed that, at early times after infections, small proportions of cells along red and white pulp divisions expressed high levels of IFN-gamma mRNA, and that these cells were depleted by protocols eliminating NK cells. The results suggest an exciting model for induction of NK cell trafficking from bone marrow to secondary compartments. This migratory pattern may localize NK cells to receive additional activation signals and/or to precisely deliver NK cell-produced cytokines.
Salazar-Mather
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Division of Biology and Medicine, Brown University, Providence, RI 02912, USA.
Ishikawa
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Biron
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D000818:Animals; D015152:Blotting, Northern; D002465:Cell Movement / Q000187:drug effects*; D002634:Chemotaxis, Leukocyte; D003433:Crosses, Genetic; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D003586:Cytomegalovirus Infections / Q000150:complications / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D017403:In Situ Hybridization; D007369:Interferon Inducers / Q000494:pharmacology*; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D008212:Lymphocyte Depletion; D016131:Lymphocyte Subsets / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000150:complications / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D011070:Poly I-C / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D016511:Severe Combined Immunodeficiency / Q000150:complications / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology* / Q000648:ultrastructure
D016207:Cytokines; D007369:Interferon Inducers; D016898:Interferon-alpha; D012333:RNA, Messenger; D007371:Interferon-gamma; D011070:Poly I-C