In situ sensory adaptation of tumor-infiltrating T lymphocytes to peptide-MHC levels elicits strong antitumor reactivity

J Immunol. 2005 Jun 1;174(11):6888-97. doi: 10.4049/jimmunol.174.11.6888.

Abstract

We have isolated from tumor-infiltrating lymphocytes (TIL) and PBL of a lung carcinoma patient several tumor-specific T cell clones displaying similar peptide-MHC tetramer staining and expressing a unique TCR. Although these clones elicited identical functional avidity and similar cytolytic potential, only T cell clones derived from TIL efficiently lysed autologous tumor cells. Interestingly, all of these clones expressed the same T cell surface markers except for the TCR inhibitory molecule CD5, which was expressed at much lower levels in TIL than in PBL. Video-imaging recordings demonstrated that, although both T cell clones could form stable conjugates with tumor cells, the Ca(2+) response occurred in TIL clones only. Significantly, analysis of a panel of circulating clones indicated that antitumor cytolytic activity was inversely proportional to CD5 expression levels. Importantly, CD5 levels in TIL appeared to parallel the signaling intensity of the TCR/peptide-MHC interaction. Thus, in situ regulation of CD5 expression may be a strategy used by CTL to adapt their sensitivity to intratumoral peptide-MHC levels.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / immunology
  • CD5 Antigens / biosynthesis
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / prevention & control
  • Cell Communication / immunology*
  • Cell Line, Tumor
  • Clone Cells
  • Cytotoxicity, Immunologic / immunology*
  • Histocompatibility Antigens Class I / biosynthesis
  • Histocompatibility Antigens Class I / metabolism*
  • Histocompatibility Antigens Class I / physiology
  • Humans
  • Immunotherapy, Adoptive / methods
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Lung Neoplasms / immunology
  • Lung Neoplasms / pathology
  • Lung Neoplasms / prevention & control
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Peptide Fragments / biosynthesis
  • Peptide Fragments / metabolism*
  • Peptide Fragments / physiology
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
  • Receptors, Antigen, T-Cell, alpha-beta / physiology
  • Signal Transduction / immunology
  • Staining and Labeling
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocyte Subsets / pathology

Substances

  • CD5 Antigens
  • Histocompatibility Antigens Class I
  • Peptide Fragments
  • Receptors, Antigen, T-Cell, alpha-beta
  • T cell receptor Vbeta8