Differential Expression of Ly6C and T-bet Distinguish Effector and Memory Th1 CD4 ⁺ Cell Properties during Viral Infection

CD4 ⁺ T cells differentiate into multiple effector types, but it is unclear how they form memory T cells during infection in vivo. Profiling virus-specific CD4 ⁺ T cells revealed that effector cells with T helper 1 (Th1) or T follicular helper (Tfh) cell characteristics differentiated into memory cells, although expression of Tfh cell markers declined over time. In contrast to virus-specific effector CD8 ⁺ T cells, increased IL-7R expression was not a reliable marker of CD4 ⁺ memory precursor cells. However, decreased Ly6C and T-bet (Tbx21) expression distinguished a subset of Th1 cells that displayed greater longevity and proliferative responses to secondary infection. Moreover, the gene expression profile of Ly6C ^loT-bet ^int Th1 effector cells was virtually identical to mature memory CD4 ⁺ T cells, indicating early maturation of memory CD4 ⁺ T cell features in this subset during acute viral infection. This study provides a framework for memory CD4 ⁺ T cell development after acute viral infection.