title: Sustained outgrowth of autotumor-reactive T lymphocytes from human ovarian carcinomas in the presence of tumor necrosis factor alpha and interleukin 2.
abstract: Tumor-infiltrating lymphocytes (TIL) freshly isolated from human ovarian carcinomas were phenotyped (up to 75% CD3+ HLA-DR+ cells) and cultured in the presence of recombinant interleukin 2 and tumor necrosis factor alpha. In short-term cultures, an initial outgrowth of CD3+ CD8+ T lymphocytes resulted in the enrichment of autotumor cytotoxicity under these culture conditions. The early peak of autotumor cytotoxicity was accompanied by interleukin 1 beta and interferon gamma production. The RNA message for interferon gamma was detected by in situ hybridization in TIL induced with interleukin 2 and tumor necrosis factor alpha but not in freshly isolated TIL. A combination of interleukin 2 and tumor necrosis factor alpha was also advantageous for selective outgrowth of CD3+ CD8+ T lymphocytes with autotumor reactivity in long-term cultures of ovarian TIL. At days 30-40 of growth, total lytic units of autotumor cytotoxicity per culture increased from a mean of 59 to 2155, and the percentage of CD3+ CD8+ T lymphocytes rose to 98% in some of the cultures. Thus, the combination of interleukin 2 and tumor necrosis factor alpha provided conditions favorable for sustained growth of autotumor-reactive CD3+ CD8+ TIL in vitro.
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pennsylvania.
authors.forename: L
authors.initials: L
authors.lastname: Vaccarello
authors.forename: Y L
authors.initials: YL
authors.lastname: Wang
authors.forename: T L
authors.initials: TL
authors.lastname: Whiteside
mesh_terms: D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D001685:Biological Factors / Q000096:biosynthesis; D016827:CD8 Antigens; D016207:Cytokines; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000276:immunology*; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D001685:Biological Factors; D016827:CD8 Antigens; D016207:Cytokines; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha