Cooperation of B cells and T cells is required for survival of mice infected with vesicular stomatitis virus

To define the role of T cells and a cells in resistance to vesscular stomatitis virus (VSV) infection, knockout mice with different specific immune defects on an identical background were infected i.v. and the outcome of infection was compared; in this way a more complete picture of the relative importance of various host defence mechanisms could be obtained, Compared to T and B cell-deficient SCID mice which all succumbed from encephalitis within 5-9 days of infection, T cell-deficient nude mice generally lived longer, but within a period of similar to 1 month after challenge all died, In contrast, B cell-deficient mice were highly susceptible even to low doses of virus and mortality could be prevented by transfer of naive a cells prior to challenge as well as by immune serum given after challenge, Analysis of MHC class I- and class II-deficient mice revealed that CD8(+) T cells could exert some antiviral activity, but CD4(+) T cells sufficed for survival and were required for optimal resistance, Consistent with this it was found that in nude mice a lethal outcome could be prevented by transfer of CD8-depleted cells from a cell-deficient mice, Thus our results clearly demonstrate that while antibodies are pivotal for survival in the early phase of VSV infection, T cells are required for long-term survival, with CD4(+) T cells being more effective in controlling this infection than CD8(+) T cells.