Interleukin 10 and dendritic cells are the main suppression mediators of regulatory T cells in human neurocysticercosis

Clin Exp Immunol. 2016 Feb;183(2):271-9. doi: 10.1111/cei.12709. Epub 2015 Nov 11.

Abstract

Neurocysticercosis is caused by the establishment of Taenia solium cysticerci in the central nervous system. It is considered that, during co-evolution, the parasite developed strategies to modulate the host's immune response. The action mechanisms of regulatory T cells in controlling the immune response in neurocysticercosis are studied in this work. Higher blood levels of regulatory T cells with CD4(+) CD45RO(+) forkhead box protein 3 (FoxP3)(high) and CD4(+) CD25(high) FoxP3(+) CD95(high) phenotype and of non-regulatory CD4(+) CD45RO(+) FoxP3(med) T cells were found in neurocysticercosis patients with respect to controls. Interestingly, regulatory T cells express higher levels of cytotoxic T lymphocyte antigen 4 (CTLA-4), lymphocyte-activation gene 3 (LAG-3), programmed death 1 (PD-1) and glucocorticoid-induced tumour necrosis factor receptor (GITR), suggesting a cell-to-cell contact mechanism with dendritic cells. Furthermore, higher IL-10 and regulatory T cell type 1 (Tr1) levels were found in neurocysticercosis patients' peripheral blood, suggesting that the action mechanism of regulatory T cells involves the release of immunomodulatory cytokines. No evidence was found of the regulatory T cell role in inhibiting the proliferative response. Suppressive regulatory T cells from neurocysticercosis patients correlated negatively with late activated lymphocytes (CD4(+) CD38(+) ). Our results suggest that, during neurocysticercosis, regulatory T cells could control the immune response, probably by a cell-to-cell contact with dendritic cells and interleukin (IL)-10 release by Tr1, to create an immunomodulatory environment that may favour the development of T. solium cysticerci and their permanence in the central nervous system.

Keywords: Taenia solium; cysticerci; dendritic cells; neurocysticercosis; regulatory T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • CTLA-4 Antigen / genetics
  • CTLA-4 Antigen / metabolism
  • Cell Communication / immunology*
  • Cell Proliferation
  • Cytokines / blood
  • Cytokines / cerebrospinal fluid
  • Dendritic Cells / immunology*
  • Female
  • Glucocorticoid-Induced TNFR-Related Protein / genetics
  • Glucocorticoid-Induced TNFR-Related Protein / metabolism
  • Host-Parasite Interactions / immunology*
  • Humans
  • Interleukin-10 / blood
  • Interleukin-10 / immunology*
  • Leukocyte Common Antigens
  • Lymphocyte Activation
  • Lymphocyte Activation Gene 3 Protein
  • Male
  • Middle Aged
  • Neurocysticercosis / immunology*
  • Phenotype
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • Taenia solium / immunology

Substances

  • Antigens, CD
  • CTLA-4 Antigen
  • Cytokines
  • Glucocorticoid-Induced TNFR-Related Protein
  • IL10 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Interleukin-10
  • Leukocyte Common Antigens
  • Lymphocyte Activation Gene 3 Protein