High frequency of virus-specific interleukin-2-producing CD4(+) T cells and Th1 dominance during lymphocytic choriomeningitis virus infection

Analysis of C57BL/6 mice acutely infected with lymphocytic choriomeningitis virus (LCMV) by using intracellular cytokine staining revealed a high freq uency (2 to 10%) of CD4(+) T cells secreting the Th1-associated cytokines i nterleukin-2 (IL-2), gamma interferon (IFN-gamma), and tumor necrosis facto r alpha, with no concomitant increase in the frequency of CD4(+) T cells se creting the Th2-associated cytokines IL-4, IL-5, and IL-10 following stimul ation with viral peptides, In LCMV-infected C57BL/6 CD8(-/-) mice, more tha n 20% of the CD4(+) T cells secreted IFN-gamma after viral peptide stimulat ion, whereas less than 1% of the CD4(+) T cells secreted IL-4 under these s ame conditions, Mice persistently infected with a high dose of LCMV clone 1 3 also generated a virtually exclusive Th1 response. Thus, LCMV induces a m uch more profound virus-specific CD4(+) T-cell response than previously rec ognized, and it is dramatically skewed to a Th1 phenotype.