High Frequency of Virus-Specific Interleukin-2-Producing CD4+T Cells and Th1 Dominance during Lymphocytic Choriomeningitis Virus Infection

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Abstract
Analysis of C57BL/6 mice acutely infected with lymphocytic choriomeningitis virus (LCMV) by using intracellular cytokine staining revealed a high frequency (2 to 10%) of CD4+T cells secreting the Th1-associated cytokines interleukin-2 (IL-2), gamma interferon (IFN-γ), and tumor necrosis factor alpha, with no concomitant increase in the frequency of CD4+T cells secreting the Th2-associated cytokines IL-4, IL-5, and IL-10 following stimulation with viral peptides. In LCMV-infected C57BL/6 CD8−/−mice, more than 20% of the CD4+T cells secreted IFN-γ after viral peptide stimulation, whereas less than 1% of the CD4+T cells secreted IL-4 under these same conditions. Mice persistently infected with a high dose of LCMV clone 13 also generated a virtually exclusive Th1 response. Thus, LCMV induces a much more profound virus-specific CD4+T-cell response than previously recognized, and it is dramatically skewed to a Th1 phenotype.