Antibodies and CD8+ T cells are complementary and essential for natural resistance to a highly lethal cytopathic virus

It is believed that CD8(+) T lymphocytes or Abs can independently clear many primary viral infections, including those caused by Orthopoxviruses (OPV), a genus that includes the human pathogens variola and monkeypox and the vaccine species vaccinia virus. However, most experiments addressing the role of Abs and CD8(+) T cells in protection have used viruses that are not specific for the host. In the present study, we used the mouse-specific OPV ectromelia virus and mice deficient in CD40, B cells, or CD8(+) T cells and adoptive transfers of CD8(+) T or B lymphocytes to show that the protection afforded by CD8(+) T cells is incomplete. Despite sustained CD8(+) T cell responses, in the absence of Ab responses ectromelia virus persists. This results in delayed disease and inexorably leads to death. Therefore, CD8(+) T lymphocytes and Abs are not redundant but complementary and essential to survive infections with a highly pathogenic viruses in the natural host.