Invariant Valpha7.2-Jalpha33 TCR is expressed in human kidney and brain tumors indicating infiltration by mucosal-associated invariant T (MAIT) cells

Int Immunol. 2008 Dec;20(12):1517-25. doi: 10.1093/intimm/dxn111. Epub 2008 Oct 16.

Abstract

The anti-tumor response of human invariant NKT (NKT) cells is well established. A novel T cell subset, mucosal-associated invariant T (MAIT) cells, possesses similar regulatory properties to NKT cells in autoimmune models and disease. Here, we examined the clonality of four T cell subsets expressing invariant alphaTCR, including Valpha7.2-Jalpha33 of MAIT cells, in 19 kidney and brain tumors. The MAIT clonotype was identified and co-expressed with NKT clonotype in half of the tumors. In contrast, two other invariant T cell clonotypes (Valpha4 and Valpha19) were not present in tumors. Such tumors also expressed Vbeta2 and Vbeta13, the restricted TCRbeta chain of MAIT cells and the antigen-presenting molecule MR1. A high percentage of infiltrating T cells was CD8+ and expressed HLA-DR suggesting activation. Although the MAIT alphaTCR was identified in both peripheral CD56+ and CD56- subsets, infiltrating lymphocytes were CD56 negative. The clonal presence of MAIT cells in tumors correlated with the expression of pro-inflammatory cytokines but no IL-4, IL-5 and IL-10, suggesting that a pro-inflammatory subset of human MAIT cells may exist. Our data imply that a CD56- subset of MAIT cells may participate in tumor immune responses similarly to NKT cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • CD56 Antigen / biosynthesis
  • CD56 Antigen / genetics
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology
  • Cell Separation
  • Cytokines / metabolism
  • Flow Cytometry
  • Gene Expression / immunology
  • Genes, T-Cell Receptor alpha / immunology
  • Glioblastoma / genetics
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • HLA-DR Antigens / biosynthesis
  • HLA-DR Antigens / genetics
  • Humans
  • Immunity, Mucosal
  • Immunohistochemistry
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology
  • Lymphocyte Activation
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Meningeal Neoplasms / genetics
  • Meningeal Neoplasms / metabolism*
  • Meningeal Neoplasms / pathology
  • Meningioma / genetics
  • Meningioma / metabolism*
  • Meningioma / pathology
  • Natural Killer T-Cells / metabolism*
  • Polymorphism, Single-Stranded Conformational
  • T-Lymphocyte Subsets / metabolism*

Substances

  • CD56 Antigen
  • Cytokines
  • HLA-DR Antigens