Symposium: Cellular Immunity and the Immunotherapy of Cancer: Tolerance and Activation: PDF OnlyCohen Peter A.; Kim, Hyun; Fowler, Daniel H.; Gress, Ronald E.; Jakoben, Michael K.; Alexander, Richard B.; Mule, James J.; Carter, Charles; Rosenberg, Steven A.Journal of Immunotherapy with Emphasis on Tumor Immunology: October 1993 Buy Abstract Summary 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 antigenpresenting 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. © Lippincott-Raven Publishers.