Comparison of cytokines and CD80 for enhancement of immunogenicity of cervical cancer cells.
Tumor cells fail to activate specific cytotoxic T lymphocytes due to lack of costimulatory molecules e.g. CD80 (B7.1). We were able to render cervical carcinoma cells immunogenic by introduction of the CD80 gene into the tumor cells. In order to enhance the efficiency of T cell activation we investigated whether addition of interleukins would augment immunostimulation by CD80. To this end, allogeneic T cells were stimulated with CD80-expressing HeLa cells or CaSki cells in the absence or presence of IL-2, IL-7, IL-12, or combinations thereof. The proliferative response of the T cells was determined. CD80-transduced HeLa or CaSki cells induced a stronger proliferative response in allogeneic T cells than parental or mock transfected control cells. All three interleukins enhanced the proliferative response of allogeneic T cells to CD80-expressing tumor cells. IL-2 or IL-7 had stronger effects in expanding the T cells than IL-12. Combination of IL-2 and IL-7 resulted in best T cell expansion. The proliferating T cells were mainly CD8+ cells with MHC class I restricted and unrestricted cytotoxic activity. Stimulation with CD80 alone or in combination with IL-7 induced mainly cytotoxic T lymphocytes. IL-2, IL-12 or the combination of IL-2 and IL-7 induced natural killer cell-like activity and specific cytolytic activity against parental and CD80-positive tumor cells. Our data suggest that the expression of both CD80 and IL-2 plus IL-7 can enhance the efficacy of tumor vaccines.
Kaufmann
A M
AM
Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Medical Center, Maywood, Illinois 60153, USA.
Gissmann
L
L
Simms
P
P
Schreckenberger
C
C
Qiao
L
L
D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002455:Cell Division; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology* / Q000494:pharmacology; D007376:Interleukin-2 / Q000276:immunology* / Q000494:pharmacology; D015851:Interleukin-7 / Q000276:immunology* / Q000494:pharmacology; D020014:K562 Cells; D008213:Lymphocyte Activation / Q000276:immunology; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000276:immunology*
D018122:B7-1 Antigen; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D015851:Interleukin-7; D018664:Interleukin-12