ROLE OF GAMMA-DELTA TCR-DIMYCOLATE-TREATED MICE TO INFLUENZA-VIRUS INFECTION( LYMPHOCYTES IN THE AUGMENTED RESISTANCE OF TREHALOSE 6,6')

Trehalose 6,6'-dimycolate (TDM), an immunomodulator, potentiates non-s pecific resistance in mice to influenza virus infection. When mice wer e injected intravenously with TDM, the striking proliferation of a min ority of T-lymphocytes bearing gamma/delta T-cell receptors (gamma del ta T-cells) that accumulated in granulomatous lungs was thought to be associated with the maintenance of acquired resistance to lethal influ enza virus infection. To clarify the cellular basis of the defence aga inst influenza virus, mice were depleted of gamma delta T-cells, alpha /beta (alpha beta) T-cells, or natural killer (NK) cells by in vivo ad ministration of corresponding antibodies prior to influenza virus infe ction. The depletion of gamma delta T-cells significantly abrogated th e augmented resistance of TDM-treated mice to infection, as did deplet ion of either alpha beta T-cells or NK cells. To gain insight into the functional ability of gamma delta T-cells, we evaluated the cytotoxic activity of this T-cell subset against a panel of target cell lines t hat were stably transfected with the influenza virus haemagglutinin (H A) gene from A/PR/8/34(H1N1) and A/Aichi/2/68(H3N2) strains. The gamma delta T-cells from TDM-treated mice showed profound cytotoxicity agai nst the target cells expressing HA of either the H1 or H3 subtype, in a non-major histocompatibility complex-restricted manner. Taken togeth er, these results indicate that gamma delta T-cells play a non-specifi c role, in conjunction with alpha beta T-cells and NK cells, in protec ting mice against influenza virus infection, and that the recognition and destruction of HA-expressing target cells by the activated gamma d elta T-cells is one of the steps involved in this anti-influenza virus immuno-surveillance.