Lymphocytes infiltrating ovarian malignant ascites: modulation of IL-2-induced proliferation by IL-4 and of selective increase in CD8+ T cells by TNF-alpha.
Lymphocytes infiltrating ovarian malignant ascites (TALs) were propagated in vitro in the presence of low (20-50 U/ml) concentrations of recombinant interleukin-2 (rIL-2) and moderate concentrations of interleukin-4 (IL-4) and tumor necrosis factor type alpha (TNF-alpha). Neither IL-4 nor TNF-alpha alone induced proliferation of ovarian TALs, but IL-4 and TNF-alpha synergized with IL-2 in enhancing the proliferation of T cells from cultures and inducing a more specific pattern of cytotoxic responses of ovarian TAL. IL-4 enhanced the proliferation of TAL cultures in the induction phase, but did not synergize with IL-2 in enhancing the proliferation and cytotoxicity of an established autologous tumor-specific CD8+/CD4- cytotoxic T lymphocyte (CTL) line. In contrast, TNF-alpha-induced preferential expansion of CD8+ CTL in TAL cultures where CD3+/CD4+ cells were initially in excess and of an established autologous tumor-specific CD8+ CTL line. This expansion resulted in increased levels of cytoxicity against autologous tumor cells. Amplification of IL-2 growth-promoting effects and selective enrichment in T cell subsets by IL-4 and TNF-alpha may therefore be useful in cellular adoptive immunotherapy using tumor-specific T cells.
Department of Gynecology, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
C G
CG
Ioannides
S
S
Rashed
B
B
Fisk
D
D
Fan
K
K
Itoh
R S
RS
Freedman
D000230:Adenocarcinoma / Q000276:immunology*; D001201:Ascites / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016827:CD8 Antigens; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4