Figure 5.

Proposed model for distinct changes of BTLA and HVEM in circulating CD4⁺ and CD8⁺ T cells. On circulating CD4⁺ and CD8⁺ T cells from healthy donors, the cis interaction between BTLA and HVEM is the predominant form, helping to maintain T cells in the naive state. In HCC patients, BTLA expressions were significantly upregulated while HVEM expression remained unchanged on circulating CD4⁺ T cells. In sharp contrast, HVEM expressions were significantly downregulated while BTLA expression remained unchanged on circulating CD8⁺ T cells. Both provide increased inhibitory signaling through BTLA engaged by intercellular HVEM in trans.