Multiple co-stimulatory molecules (CD28, CD27, OX40, and 4-1BB) (128–130) and co-inhibitory receptors [B− and T−lymphocyte attenuator (BTLA), T cell immunoglobulin and mucin domain-containing-3 (TIM-3), CTLA-4, T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT), LAG-3, PD-1, and Nrp-12] (15, 50, 57, 77, 93, 131) that transmit various secondary signals play a pivotal role in the heterogeneous characteristics of Tregs and may contribute to Tregs-induced dysfunction of the whole immune system in sepsis, especially imbalanced Tregs/Tconvs (15, 74–77, 83, 132, 133). The gene discussed is PDCD1; the disease is Sepsis.