Propagation of Mouse and Human T Cells with Defined Antigen Specificity and Function

  1. Derek J. Chadwick Organizer and
  2. Joan Marsh
  1. Peter A. Cohen1,
  2. Daniel H. Fowler2,
  3. Hyun Kim1,
  4. Richard L. White1,
  5. Brian J. Czerniecki1,
  6. Charles Carter3,
  7. Ronald E. Gress2 and
  8. Steven A. Rosenberg1

Published Online: 28 SEP 2007

DOI: 10.1002/9780470514672.ch12

Ciba Foundation Symposium 187 - Vaccines Against Virally Induced Cancers

Ciba Foundation Symposium 187 - Vaccines Against Virally Induced Cancers

How to Cite

Cohen, P. A., Fowler, D. H., Kim, H., White, R. L., Czerniecki, B. J., Carter, C., Gress, R. E. and Rosenberg, S. A. (2007) Propagation of Mouse and Human T Cells with Defined Antigen Specificity and Function, in Ciba Foundation Symposium 187 - Vaccines Against Virally Induced Cancers (eds D. J. Chadwick and J. Marsh), John Wiley & Sons, Ltd., Chichester, UK. doi: 10.1002/9780470514672.ch12

Author Information

  1. 1

    Surgery Branch, Building 10, Room 2B56, National Cancer Institute, Bethesda, MD 20892, USA

  2. 2

    Experimental Immunology Branch, Division of Cancer Biology and Diagnosis, Bethesda, MD 20892, USA

  3. 3

    Department of Transfusion Medicine, Warren Grant Magnuson Clinical Center, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA

Publication History

  1. Published Online: 28 SEP 2007

ISBN Information

Print ISBN: 9780471950264

Online ISBN: 9780470514672

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Keywords:

  • mouse propagation;
  • human T cells;
  • antigen specificity;
  • allograft facilitation;
  • antigen-presenting cells

Summary

Difficulties maintaining fully functional CD4+ T cells in culture have historically limited the study of their role in tumour rejection as well as other clinical applications. As the therapeutic value of current antitumour CD8+ T cell adoptive therapy becomes better defined, a strong impetus exists to determine optimal conditions for culturing antitumour CD4+ T cells. Our goal is to promote broadly polyclonal, antigen-specific CD4+ T cell responses of either Th1 or Th2 character for use in antitumour therapy or allograft facilitation, respectively. Similar obstacles exist in murine and human cultures: (1) during even brief periods of culture CD4+ T cells develop high ‘background’ reactivity to class II-positive antigen-presenting cells; (2) maintenance of antigen specificity as evidenced by cytokine secretion and short-term proliferation assays is insufficient to ensure bulk numerical expansion; (3) Th1-type CD4+ T cells often lose their potential for antigen-specific secretion of interleukin 2 on re-stimulation (though remain inducible by 12-0-tetradecanoylphorbol 13-acetate/ionomycin); (4) during prolonged culture selection pressure favours CD4+ subpopulations that recognize artifactual antigens such as culture medium proteins; (5) even with optimal culture conditions, cultured CD4+ T cells may function differently in vivo to uncultured CD4+ T cells. We have devised various strategies to surmount these obstacles by use of selected cytokines, antigen-presenting cells and timely culture manoeuvres.