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Activation of preexisting t cell clones by targeted interleukin 2 therapy

Academic Article
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Overview

authors

  • Straten, P. T.
  • Guldberg, P.
  • Seremet, T.
  • Reisfeld, Ralph
  • Zeuthen, J.
  • Becker, J. C.

publication date

  • July 1998

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • The induction of an immunological antitumor response capable of eradicating metastatic tumors is the ultimate goal of immunotherapy. We have recently shown that this can be achieved by interleukin 2 (IL-2) therapy directed to the tumor microenvironment by a recombinant antibody-IL-2 fusion protein. It is not known, however, whether this curative treatment is associated with a predominance of T cells carrying specific T cell receptor variable beta regions (TCRBV) or the presence of clonally expanded T cells. To address this question, we have used a quantitative reverse transcriptase-coupled PCR method to analyze the TCRBV region repertoire in tumor-infiltrating lymphocytes of treated and untreated animals. As controls the TCRBV region repertoire was analyzed in blood and skin from disease-free animals. The results indicate an overexpression of TCRBV5 in the tumors of all treated mice and an additional overexpression of individual regions in each tumor. Direct sequencing of these TCRBV regions did not reveal any evidence of clonal expansions. However, since clonal expansions could exist as subpopulations in highly expressed regions, not detectable by direct sequencing, a denaturing gradient gel electrophoresis assay was used for clonal analysis of TCRBV PCR products. Denaturing gradient gel electrophoresis analysis of selected TCRBV regions revealed the presence of clonotypic T cells in tumors from both treated and untreated animals. These data indicate that targeted IL-2 therapy in this model does not induce clonal T cell responses de novo, rather it acts as an activator for an already existing population of clonotypic T cells.

subject areas

  • Animals
  • Base Sequence
  • Clone Cells
  • DNA Primers
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Interleukin-2
  • Lymphocyte Activation
  • Melanoma, Experimental
  • Mice
  • Mice, Inbred C57BL
  • Polymerase Chain Reaction
  • T-Lymphocytes
  • Tumor Cells, Cultured
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Identity

PubMed Central ID

  • PMC21154

International Standard Serial Number (ISSN)

  • 0027-8424

PubMed ID

  • 9671756
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Additional Document Info

start page

  • 8785

end page

  • 8790

volume

  • 95

issue

  • 15

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