Propagation of mouse and human T cells with defined antigen specificity and function.
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-O-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.
Cohen
P A
PA
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Fowler
D H
DH
Kim
H
H
White
R L
RL
Czerniecki
B J
BJ
Carter
C
C
Gress
R E
RE
Rosenberg
S A
SA
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D006801:Humans; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D009374:Neoplasms, Experimental / Q000276:immunology; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
D000939:Epitopes; D011994:Recombinant Proteins; D007371:Interferon-gamma