Human T cell crosstalk is induced by tumor membrane transfer

PLoS One. 2015 Feb 11;10(2):e0118244. doi: 10.1371/journal.pone.0118244. eCollection 2015.

Abstract

Trogocytosis is a contact-dependent unidirectional transfer of membrane fragments between immune effector cells and their targets, initially detected in T cells following interaction with professional antigen presenting cells (APC). Previously, we have demonstrated that trogocytosis also takes place between melanoma-specific cytotoxic T lymphocytes (CTLs) and their cognate tumors. In the present study, we took this finding a step further, focusing on the ability of melanoma membrane-imprinted CD8+ T cells to act as APCs (CD8+ T-APCs). We demonstrate that, following trogocytosis, CD8+ T-APCs directly present a variety of melanoma derived peptides to fraternal T cells with the same TCR specificity or to T cells with different TCRs. The resulting T cell-T cell immune synapse leads to (1) Activation of effector CTLs, as determined by proliferation, cytokine secretion and degranulation; (2) Fratricide (killing) of CD8+ T-APCs by the activated CTLs. Thus, trogocytosis enables cross-reactivity among CD8+ T cells with interchanging roles of effectors and APCs. This dual function of tumor-reactive CTLs may hint at their ability to amplify or restrict reactivity against the tumor and participate in modulation of the anti-cancer immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigen-Presenting Cells / immunology
  • Antigens, Neoplasm / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Line, Tumor
  • Cell Membrane / metabolism*
  • Female
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Immunomodulation
  • Melanoma / immunology*
  • Melanoma / pathology*
  • Mice
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Antigens, Neoplasm
  • Histocompatibility Antigens Class II

Grants and funding

The work was supported by the following: 1. AMRF, Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, URL: http://www.adelsonfoundation.org/amrfphil.html, Author: ML; 2. DFG, Deutsche Forschungsgemeinschaft; URL: http://www.dfg.de/en/research_funding/index.html, Grant number:trilateral project SCHU 1186/9-1, Author: ML; and 3. ICA, Israel Cancer Association, URL: http://en.cancer.org.il/, Grant number: 20130060-B, Author: ML. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.