Sex-Dependent, Early Cytokine Production by NK-Like Spleen Cells Following Infection with the D Variant of Encephalomyocarditis Virus (EMCV-D)

Spleen cell cultures from diabetes-resistant ICR Swiss females exhibited an increase in expression of Ia antigens 24 hours post-infection (PI) with EMCV-D while comparable spleen cell cultures from diabetes-susceptible males of this strain did not exhibit this increase in Ia antigens expression. A monoclonal antibody specific for mouse interferon-gamma (IFN gamma) eliminated this increase in Ia antigens expression. Interferon-gamma (IFN gamma) and interleukin 2 (IL-2) production by EMCV-D-infected spleen cell cultures were monitored at 4-hour intervals for 24 hours. Female spleen cells produced IFN gamma earlier (less than 16 hours PI) and in greater amounts than did comparably treated male spleen cells. Addition of a monoclonal rat anti-mouse IL-2 to virus-infected cultures did not significantly affect the early (less than 16 hours PI) production of IFN gamma by spleen cells of females. Treatment of the spleen cell donors with rabbit anti-asialo GM1 (AAGM1) abolished early production of IFN gamma in virus-infected female spleen cell cultures and reduced the early IL-2 production by infected male and female cells. These results suggest that an NK-like cell is responsible for the early female IFN gamma production; this may be a factor in the resistance of female ICR Swiss mice to EMCV-D-induced diabetes.