INTRACELLULAR IFN-GAMMA EXPRESSION IN NATURAL-KILLER-CELLS PRECEDES LUNG CD8(-CELL RECRUITMENT DURING RESPIRATORY SYNCYTIAL VIRUS-INFECTION() T)

Natural killer (NK) cells are recruited locally during the initial pha ses of virus infection and produce cytokines which may affect the subs equent emergence of specific T cells. In this study, cellular response s to primary respiratory syncytial virus (RSV) infection and after vac cination with individual viral proteins were investigated in BALB/c mi ce using the new NK cell antibody, DX5, Purified DX5(+) cells caused l ysis of YAC-1 cell targets. DX5(+) cells did not express CD8, CD45R or MHC class II antigens, A small proportion of DX5(+) cells coexpressed CD4 (10.3%) and CD3 (10.6%). Of the DX5(+)/CD4(+) cells, the majority expressed the alpha/beta T cell receptor and less than 1 % expressed the gamma/delta T cell receptor. During infection with RSV, lung DX5()/CD3(-) Nh cells peaked on day 4 of primary infection and were the mo st numerous subset producing IFN-gamma, as determined by intracellular staining, at this time-point. Less than 1% of the DX5(+) cells secret ing IFN-gamma were CD4(+). In the lungs of mice vaccinated with recomb inant vaccinia virus expressing individual RSV proteins, increased NK cell cytotoxicity and IFN-gamma production correlated with increased n umbers of CD8(+) T cells. Mice with few NK cells subsequently had low CD8(+) T cells and developed lung eosinophilia, IFN-gamma-producing Nh cells therefore form a substantial component of the early cellular re sponse to virus infection with important potential influences on the s ubsequent development of specific immunity.