Enrichment of LAG-3, but not PD-1, on double negative T cells at the female genital tract

Am J Reprod Immunol. 2014 Dec;72(6):534-40. doi: 10.1111/aji.12308. Epub 2014 Aug 25.

Abstract

Problem: The expression of inhibitory markers such as LAG-3 and PD-1 on T lymphocytes regulates immune function. Their expression at the genital mucosa is poorly understood, but regulation of immune activation at the female genital tract likely controls susceptibility to sexually transmitted infections.

Method of study: Cervical mononuclear cells were phenotyped by flow cytometry. Concentrations of cytokines were determined in cervical-vaginal lavage samples by bead array.

Results: LAG-3 expression was significantly elevated at the genital mucosa and was associated with expression of CCR5 and CD69. Double negative (DN) T cells expressed the highest levels of LAG-3, but not PD-1, and were more activated than other T lymphocytes.

Conclusion: The elevated expression of LAG-3 at the genital tract suggests it may regulate T-cell activation, and identify cells susceptible to HIV infection. The enrichment of LAG-3 on DN T cells suggests LAG-3 may contribute to the immunoregulatory activity of these cells.

Keywords: Cervical; HIV; LAG-3; exhaustion; sexually transmitted infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • CD4 Antigens / metabolism
  • CD8 Antigens / metabolism
  • Cell Separation
  • Cervix Uteri / immunology*
  • Female
  • Flow Cytometry
  • HIV / immunology*
  • HIV Infections / immunology*
  • Humans
  • Lectins, C-Type / metabolism
  • Lymphocyte Activation
  • Lymphocyte Activation Gene 3 Protein
  • Programmed Cell Death 1 Receptor / metabolism*
  • Receptors, CCR5 / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / virology

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CCR5 protein, human
  • CD4 Antigens
  • CD69 antigen
  • CD8 Antigens
  • Lectins, C-Type
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Receptors, CCR5
  • Lymphocyte Activation Gene 3 Protein