Use of interleukin-7, interleukin-2, and interferon-γ to propagate CD4+T cells in culture with maintained antigen specificity

Peter A. Cohen, Hyun Kim, Daniel H. Fowler, Ronald E. Gress, Michael K. Jakobsen, Richard B. Alexander, James J. Mulé, Charles Carter, Steven A. Rosenberg

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

In contrast to CD8+T cells, it has been difficult to establish consistently satisfactory conditions for the bulk culture of antitumor CD4+T cells in either mice or humans. This difficulty is not limited to tumor antigen, since similar problems are encountered growing CD4+T cells that recognize alloantigen, tetanus, or candida. Four basic findings are reviewed in this article, stemming from work with identical results in both human and mouse. (a) Although CD4+T cells initially proliferate after exposure to appropriate antigen-presenting cells (APCs), such proliferation is not sustained; however, expansion of CD4+T cells can be achieved with the addition of recombinant interleukin-2 (rIL2) or rIL-7. (b) Specific CD4+responses to antigens are often better sustained with exogenous IL-7 than with exogenous IL-2. (c) Adding rIL-7 or rIL-2 permits sustained CD4+T-cell proliferation, but subsequent culture restimulation is complicated by high background reactivity to APCs whether APCs are antigen pulsed or not; this problem can be overcome by addition of exogenous interferon-γ (IFN-γ) to the CD4+cultures. (d) In certain instances proliferation is paradoxically impaired by reexposure to specific antigen, possibly reflecting apoptosis; this problem is also overcome by addition of rINF-γ to culture. We conclude that combinations of exogenous IL-7, IL-2, and IFN-γ with APC restimulation can be used to sustain antigen-specific CD4+T cells in culture. Using these techniques, antitumor CD4+T cells were propagated from the peripheral blood of two tumor-bearing patients.

Original languageEnglish (US)
Number of pages1
JournalJournal of Immunotherapy
Volume14
Issue number3
DOIs
StatePublished - Oct 1993

Keywords

  • CD4T cells
  • Dendritic cells
  • Interferon-γ
  • Interleukin-7

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

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