Lymphotoxin-β-deficient mice show defective antiviral immunity

Lymphotoxin beta (LT beta), a member of the tumor necrosis factor family, plays an important role in lymphoid organogenesis. In order to determine whether LT beta is involved in cellular immunity, we investigated the antiviral immune response of LT beta-deficient (LT beta -/-) 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 LT beta-deficient T lymphocytes and dendritic cells were intact. Reconstitution of irradiated LT beta +/+ mice with LT beta -/- bone marrow induced a disorganized splenic structure, accompanied by impairment of the LCMV-specific CTL response. These data indicate that the absence of LT beta 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. (C) 1999 Academic Press.