The Effects of Anti-LAP Monoclonal Antibody Down-regulation of CD4+LAP+ T Cells on Allogeneic Corneal Transplantation in Mice

Sci Rep. 2018 May 22;8(1):8021. doi: 10.1038/s41598-018-26235-5.

Abstract

CD4+latency-associated peptide (LAP)+ T cells are a newly discovered T cell subset with suppressive function on immune responses. In this study, we investigate the role of CD4+LAP+ T cells on mice corneal allograft survival by down-regulating their expression using anti-LAP mAb. We show that a blockage of LAP leads to a decrease in the percentage of T cells expressing CD4+Foxp3+, CD4+GARP+, CD4+LAP+ and CD4+IL-10+ in the lymph nodes and spleens of mice undergoing orthotopic penetrating transplantation of corneal allograft, without affecting corneal graft survival. In addition, higher percentages of CD4+IFN-γ+ and CD4+IL-17A+ T cells in the lymph nodes and spleens, as well as TNF, IFN-γ, IL-17A and IL-6 levels in the aqueous humor, significantly increase in mice with rejected corneal grafts. The expression of TGF-β1 decreases in corneal grafts during corneal rejection period. It is therefore possible that anti-LAP mAb can down-regulate the regulatory T cell subsets with its immunosuppressive effects. The rejection of corneal grafts seems to mainly be associated with the up-regulation of Th1 and Th17 cell subsets in peripheral lymph nodes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibody-Dependent Cell Cytotoxicity* / drug effects
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cornea / drug effects
  • Cornea / immunology
  • Corneal Transplantation / adverse effects
  • Corneal Transplantation / methods*
  • Down-Regulation
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control
  • Graft Survival / drug effects
  • Graft Survival / immunology
  • Immune Tolerance / drug effects
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Peptides / immunology*
  • Peptides / metabolism*
  • Protein Precursors / immunology*
  • Protein Precursors / metabolism*
  • Transforming Growth Factor beta / immunology*
  • Transforming Growth Factor beta / metabolism*
  • Transplantation Immunology / drug effects
  • Transplantation, Homologous

Substances

  • Antibodies, Monoclonal
  • Peptides
  • Protein Precursors
  • Transforming Growth Factor beta
  • latency-associated propeptide, TGF-beta