IL-2-dependent NK cell responses discovered in virus-infected beta 2-microglobulin-deficient mice.
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.
Su
H C
HC
Division of Biology and Medicine, Brown University, Providence, RI 02912.
Orange
J S
JS
Fast
L D
LD
Chan
A T
AT
Simpson
S J
SJ
Terhorst
C
C
Biron
C A
CA
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*
D007376:Interleukin-2; D001613:beta 2-Microglobulin; D016572:Cyclosporine