CD4+PD-1+ T cells acting as regulatory cells during the induction of anterior chamber-associated immune deviation

Invest Ophthalmol Vis Sci. 2006 Oct;47(10):4444-52. doi: 10.1167/iovs.06-0201.


Purpose: To study the expression and functional characteristics of programmed death-1 (PD-1) and its ligands in the spleens of mice undergoing anterior chamber-associated immune deviation (ACAID).

Methods: ACAID was induced in BALB/c mice by intracameral injection of ovalbumin (OVA). The expression of PD-1 and its ligands in the spleens of ACAID mice was determined by quantitative real-time PCR, Western blotting, and flow cytometry. In vitro proliferation assays, enzyme-linked immunosorbent assays, and adoptive transfer assays were used to investigate the functional characteristics of splenic CD4+PD-1+ T cells of ACAID mice.

Results: Both mRNA and protein of PD-1, PD-L1, and PD-L2 were markedly upregulated in the spleens of ACAID mice compared with controls. CD4+PD-1+ T cells from ACAID mice produced large amounts of IL-10 and exhibited in vitro antigen-specific suppressive activity. CD4+PD-1+ T cells from ACAID mice were able to significantly inhibit the antigen-specific, delayed-type hypersensitivity response when adoptively transferred to naive mice.

Conclusions: CD4+PD-1+ T cells from ACAID mice, as regulatory cells, are involved in the induction of antigen-specific suppression in association with enhanced expression of IL-10. CD4+PD-1+ T cells in the murine spleen may represent a substantial population of regulatory T cells possibly responsible for the induction of ACAID after intracameral injection of antigen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Anterior Chamber / immunology*
  • Antigens, Surface / genetics
  • Antigens, Surface / immunology*
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / immunology*
  • B7-1 Antigen / genetics
  • B7-1 Antigen / metabolism
  • B7-H1 Antigen
  • Blotting, Western
  • CD4 Antigens / immunology*
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Hypersensitivity, Delayed / immunology
  • Interleukin-10 / metabolism
  • Lymphocyte Activation / immunology
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin
  • Peptides / genetics
  • Peptides / metabolism
  • Phenotype
  • Programmed Cell Death 1 Receptor
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spleen / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • Up-Regulation
  • Uveitis, Anterior / immunology*


  • Antigens, Surface
  • Apoptosis Regulatory Proteins
  • B7-1 Antigen
  • B7-H1 Antigen
  • CD4 Antigens
  • Cd274 protein, mouse
  • Membrane Glycoproteins
  • Pdcd1 protein, mouse
  • Peptides
  • Programmed Cell Death 1 Receptor
  • RNA, Messenger
  • Interleukin-10
  • Ovalbumin