CD8⁺ type-2 T cells enhance the severity of acute herpes virus infection in mice

The role of CD8⁺ suppressor T cells in acute herpes simplex virus type 1 (HSV) infection was investigated in mice. CD8⁺ CD11b⁺ TCR-γ/δ⁺ suppressor T cells (HSV-STC) were demonstrated in spleens of mice infected intraperitoneally (i.p.) with HSV. When HSV-STC from mice infected with a 10 LD₅₀ of HSV (donors) were adoptively transferred to mice 3 days after being infected with a 1 LD₅₀ dose of HSV (recipients), the morbidity and mortality of recipients were greatly increased (mean survival time in days (MSD): 9.4 days; mortality, 100%) as compared with controls that received CD4⁺ T cells or a whole T-cell lysate from donors (MSD, > 19.6 days or > 19.1 days; mortality, 38% or 50%). The morbidity and mortality of mice exposed to a 1 LD₅₀ of HSV were also increased when they were continuously treated with recombinant murine IL-4. However, the survival rate of mice exposed to a 10 LD₅₀ of HSV increased after multiple treatments of these mice with anti-IL-4 monoclonal antibody. IL-4-producing cells were detected in a population of HSV-STC, and IL-4 was produced when these cells were cultured in the presence of UV-inactivated HSV in vitro. These results indicate that IL-4 plays an important role in the progression of acute HSV infection and, through the production of IL-4, HSV-STC may increase the severity of the acute-phase infection of HSV in mice.