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

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)89-98
Number of pages10
JournalCellular Immunology
Volume230
Issue number2
DOIs
StatePublished - Aug 2004
Externally publishedYes

Keywords

  • Costimulation
  • Dendritic cells
  • Human T cells
  • Memory T cells
  • Myelin basic protein
  • Naïve T cells
  • PD-1
  • PD-1 ligand

Fingerprint

Dive into the research topics of 'PD-1 ligands, negative regulators for activation of naïve, memory, and recently activated human CD4 + T cells'. Together they form a unique fingerprint.

Cite this