The research described in this proposal is designed to explore the mechanisms involved in the depression of cell-mediated immunity by acute viral infection. The approach outlined will permit the development of a suitable animal model for the study of this question by infecting rats with a wild or attenuated virus strain after producing tuberculin (PPD) sensitivity. The two main cellular components of the delayed hypersensitivity reaction, the sensitized lymphocyte and the immunologically non-specific phagocytic cell of bone marrow origin will be studied both in vivo and in vitro. The effect of virus infection on circulatang lymphocyte levels and specifically on thymus dependent lymphocyte levels will be assessed by means of peripheral cell counts and the use of heterologous anti-thymus cell antisera. Adoptive transfer experiments to determine the functional capacities of the two cell types in reconstitution of irradiated recipients will be conducted and will be combined with assay of donor cells and of recipients for virus by co-cultivation techniques. This will permit evaluation of the functional integrity of each cellular component and will provide information regarding viral persistence in maintaining the state of suppression. In vitro evaluation of lymphocyte function will be measured by non-specific (Phytohemagglutinin) and specific (PPD) blastogenic response and by determining the ability of lymphocytes from suppressed animal to produce macrophage migration inhibition factor (MIF) upon contact with specific antigen. The macrophages of suppressed animals will be evaluated for their response to MIF compared to the macrophages from non-infected animals.