Delayed Elimination of the LCM Virus from Acid Sphingomyelinase‐Deficient Mice due to Reduced Expansion of Virus‐Specific CD8(+) T Lymphocytes

Utermöhlen, O.; Karow, U.; Baschuk, N.; Herz, J.; Loegters, T. T.; Krönke, M.

The phagolysosomally localized acid sphingomyelinase (ASMase) activated by proinflammatory cytokines such as TNF and IFN‐γ generates the signalling molecule ceramide which in turn results in the activation of proteases like cathepsin D. These characteristics of ASMase suggest a possible role of this molecule in the phagocytotic uptake and phagosomal degradation processes of antigens or in antigen presentation. We show here that ASMase(–/–) mice fail to eliminate the noncytopathic lymphocytic choriomeningitis (LCM) virus as rapidly as littermate wildtype mice. Investigation of the immune response revealed a reduced expansion of CD8(+) T cells. The secretion of IFN‐γ in response to contact with target cells as well as the cytolytic activity of virus‐specific CD8(+) T cells was severely impaired. Additionally, both phases of the LCM virus‐specific DTH response, mediated by CD8(+) and CD4(+) T cells consecutively, were diminished in ASMase(–/–) mice. However, the secondary memory response of virus‐specific CTL was not altered, and the virus was effectively controlled for at least 3 months by ASMase(–/–) mice. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus‐specific CD8(+) T cells during the acute infection of mice with the LCM virus.