Lymphotoxin-β-Deficient Mice Show Defective Antiviral Immunity

Lymphotoxin β (LTβ), a member of the tumor necrosis factor family, plays an important role in lymphoid organogenesis. In order to determine whether LTβ is involved in cellular immunity, we investigated the antiviral immune response of LTβ-deficient (LTβ −/−) mice to lymphocytic choriomeningitis virus (LCMV). Cytotoxic T lymphocyte (CTL) responses to LCMV were severely diminished, leading to viral persistence in brain and kidney. However, major functions of LTβ-deficient T lymphocytes and dendritic cells were intact. Reconstitution of irradiated LTβ +/+ mice with LTβ −/− bone marrow induced a disorganized splenic structure, accompanied by impairment of the LCMV-specific CTL response. These data indicate that the absence of LTβ does not affect the intrinsic function of T lymphocytes or of dendritic cells but that the structural integrity of the spleen is strongly associated with generation of antiviral immunity.