Elevated IL-10 in the serum from infected mice was related to the occurrence of lymphopenia, and the knocking out of IL-10 and blocking IL-10/IL-10R signaling prevent lymphopenia via inhibiting apoptosis, trafficking, and the expression of coinhibitory molecules of lymphocytes, which contributes to enhancing the survival of mice infected with FMDV. This evidence concerns the gene IL10RA and lymphopenia.