Induction of interleukin-2 receptor by tumor necrosis factor alpha on cultured ovarian tumor-associated lymphocytes.
We have recently reported that autologous tumor-specific cytotoxic T lymphocyte (CTL) lines and clones can be developed from lymphocytes infiltrating ovarian malignant ascites (TAL). In this study, we investigated the biological effects of tumor necrosis factor alpha (TNF alpha) in the induction, expansion, long-term proliferation and lytic function of CD8+ TAL. TNF alpha up-regulated the IL-2 receptor (IL-2R) alpha chain (Tac antigen) on the surface of CD3+ CD8+ CD4- TAL, enhanced the proliferation of autologous tumor-specific CTL, and potentiated their lytic function in long-term cultures. Furthermore, in the induction and expansion phase of CD8+ TAL, the presence of TNF alpha was associated with a selective increase in CD8+ IL-2R+ (Tac+) cells, and subsequent decrease in CD4+ IL-2R+ (Tac+) cells. These results suggest that the observed facilitation of the outgrowth of CD8+ cells in TAL cultures may be due, at least in part, to the up-regulation of IL-2R, and indicate the usefulness of TNF alpha in the analysis of signalling in autologous tumor-reactive CTL.
Ioannides
C G
CG
Department of Gynecology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Fisk
B
B
Tomasovic
B
B
Pandita
R
R
Aggarwal
B B
BB
Freedman
R S
RS
D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D017252:CD3 Complex; D016827:CD8 Antigens / Q000502:physiology; D002478:Cells, Cultured; D004357:Drug Synergism; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D046911:Macromolecular Substances; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology / Q000648:ultrastructure; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D046911:Macromolecular Substances; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha