Heterogeneity and plasticity of the naive CD4+ T cell compartment

• Five naive CD4 + T subsets (T Q , T MEM , T TCR , T IFN , and T UND ) emerge during thymic maturation • Naive T cell subsets display divergent functional programs and differentiation potential • Lupus patients show elevated interferon-stimulated gene expression Five naive CD4 + T subsets (T Q , T MEM , T TCR , T IFN , and T UND ) emerge during thymic maturation Naive T cell subsets display divergent functional programs and differentiation potential Lupus patients show elevated interferon-stimulated gene expression This study describes the transcriptional heterogeneity of murine and human naive CD4 + T cells as comprising multiple discrete clusters that impact CD4 + T cell fate and trajectories. Naive CD4 + T cells experiencing inflammatory environments exhibit an altered transcriptional state that biases their differentiation trajectories.