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 s tudied in CD8(+) T cell-deficient mice. On day 7 after infection, dram atically elevated splenic NK cell activities were observed in both bet a(2)-microglobulin-negative (beta(2)-m(-/-)) mice deficient in CD8(+) T cells and anti-CD8-treated C57BL/6 animals. The enhanced responses c ould be attributed to increased numbers of activated NK1.1(+)CD3(-) ce lls. The day 7 NK cell responses in beta(2)-m(-/-) mice, but not in no rmal 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 N K cell activation. Taken together, these results showed that NK cells can be activated and expanded by an IL-2-dependent pathway. Because th ese responses can only be measured in the absence of CD8(+) T lymphocy tes, an exciting model of networking between T and NK cells in respons e to viruses is postulated.