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PD-1 ligands, negative regulators for activation of naïve, memory, and recently activated human CD4+ T cells

2004; Elsevier BV; Volume: 230; Issue: 2 Linguagem: Inglês

10.1016/j.cellimm.2004.09.004

1090-2163

Guifang Cai, Arnon Karni, Enedina Maria Lobato de Oliveira, Howard L. Weiner, David A. Hafler, Gordon J. Freeman,

T-cell and B-cell Immunology

We examined the role of the PD-1 pathway on the activation of naïve, memory, and recently activated human CD4+ T cells to test whether they responded differently. PD-1 ligand blockade modestly enhanced the percentage of responding T cells and production of IFN-γ in a primary response to myelin basic protein (MBP) in normal donors. PD-1 ligand blockade strongly enhanced proliferation and cytokine production by memory or recently activated T cells (tetanus toxoid and MBP). Blockade of PD-L1 alone had more effect than PD-L2, consistent with its higher expression on ex vivo dendritic cells; furthermore, anti-PD-L1 plus anti-PD-L2 resulted in the greatest enhancement. Moreover, PD-L1-Ig inhibited anti-CD3 induced activation of naïve, memory, and recently activated CD4+ T cells. Together, our data demonstrated PD-1 functioned as a negative regulatory pathway on naïve T cells during a primary response, and more potently, on memory or recently activated T cells during a secondary response.