To determine whether the reduced population of EM CD4 T cells in ICOS−/− mice was associated with reduced protection to re-infection, we infected Balb/c and ICOS−/− mice with the influenza virus Hkx31, rested the mice for over 30 days, then challenged with the more lethal strain of influenza, PR8 (Figure 5F). Here, ICOS is linked to influenza.