A pathogenic role of Th2 responses on the severity of encephalomyelitis induced in mice by herpes simplex virus type 2 infection

A pathogenic role of Th2 cells and their cytokine products (IL-4 and IL- 10, Th2 cytokines) on the development of herpes simplex myelitis (HSM) was studied in mice exposed to footpad injection of herpes simplex virus type 2 (HSV-2). Morbidity and mortality of mice with HSM (HSM mice) increased when they were treated with a mixture of Th2 cytokines. Additionally, survival rates of HSM mice increased when they were treated with a mixture of mAbs for Th2 cytokines. As compared with HSM mice treated with saline, the growth of HSV-2 in spinal cords of HSM mice treated with the mixture of Th2 cytokines increased. Th2 cells (myelitis-associated Th2 cells, MTh2 cells) were demonstrated among cerebrospinal fluid cells from HSM mice. After the stimulation with HSV-2 antigen (Ag), MTh2 cells from HSM mice previously treated with the mixture of Th2 cytokines produced enhanced amounts of Th2 cytokines into their culture fluids, as compared with the amount of Th2 cytokines produced by MTh2 cells. Th2 cells were also demonstrated in mononuclear cells from spleens of HSM mice. When compared with HSM mice inoculated with splenic CD4⁺ T cells from normal mice, morbidity and mortality of HSM mice inoculated with MTh2 cells markedly increased. These results indicated that the severity of HSM induced in mice by footpad injection of HSV-2 was influenced by MTh2 cells or Th2 cytokines released from these MTh2 cells. Th2 responses manifested in mice by HSV-2 infection may act as a pathogenic enhancer of HSM severities.