title: IL-2-dependent NK cell responses discovered in virus-infected beta 2-microglobulin-deficient mice.
abstract: In vivo NK cell responses to lymphocytic choriomeningitis virus were studied in CD8+ T cell-deficient mice. On day 7 after infection, dramatically elevated splenic NK cell activities were observed in both beta 2-microglobulin-negative (beta 2-m-/-) mice deficient in CD8+ T cells and anti-CD8-treated C57BL/6 animals. The enhanced responses could be attributed to increased numbers of activated NK1.1+CD3- cells. The day 7 NK cell responses in beta 2-m-/- mice, but not in normal C57BL/6 animals, were cyclosporin A sensitive and coincided with IL-2 production and high affinity IL-2R expression on NK cells. Proof that IL-2 played an essential role in day 7 responses was provided by the observation that IL-2-/- x beta 2-m-/- mice lacked the late NK cell activation. Taken together, these results showed that NK cells can be activated and expanded by an IL-2-dependent pathway. Because these responses can only be measured in the absence of CD8+ T lymphocytes, an exciting model of networking between T and NK cells in response to viruses is postulated.
authors.affiliation: Division of Biology and Medicine, Brown University, Providence, RI 02912.
authors.forename: H C
authors.initials: HC
authors.lastname: Su
authors.forename: J S
authors.initials: JS
authors.lastname: Orange
authors.forename: L D
authors.initials: LD
authors.lastname: Fast
authors.forename: A T
authors.initials: AT
authors.lastname: Chan
authors.forename: S J
authors.initials: SJ
authors.lastname: Simpson
authors.forename: C
authors.initials: C
authors.lastname: Terhorst
authors.forename: C A
authors.initials: CA
authors.lastname: Biron
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016572:Cyclosporine / Q000494:pharmacology; D003601:Cytotoxicity Tests, Immunologic; D005434:Flow Cytometry; D007376:Interleukin-2 / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D013154:Spleen / Q000166:cytology; D001613:beta 2-Microglobulin / Q000172:deficiency*
chemical_list: D007376:Interleukin-2; D001613:beta 2-Microglobulin; D016572:Cyclosporine