Analysis of cytotoxic activity of the CD4+ T lymphocytes generated by local immunotherapy.
We previously reported that the anti-tumour effect of OK-432 is considerably enhanced by its intratumoral injection together with fibrinogen. In the present study, we generated killer T cells by culturing tumour-infiltrating lymphocytes from thyroid cancer patients who had received this local immunotherapy. Phenotypic analysis revealed that the T cells were positive for CD3+, CD4+, Leu8-, CD45RO+ and T-cell receptor (TCR)alpha beta+, as well as showing strong surface expression of HLA-DR, CD25, LFA-1 and ICAM-1. The generated CD4+ T cells secreted interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, TNF-beta, and interleukin (IL)-6 (but not IL-4), and exhibited a high level of cytolytic activity against several tumour cell lines. The cytolytic activity of these T cells for Daudi cells was inhibited by preincubation with an anti-intercellular adhesion molecule (ICAM)-1 antibody, but not by preincubation with anti-TCR alpha beta, anti-CD2, or anti-LFA-1 antibodies. Pretreatment with anti-ICAM-1 antibody inhibited T-cell cytolytic activity, but not conjugation with target cells. In addition, incubation with immobilised anti-ICAM-1 enhanced the secretion of IFN-gamma by T cells. We conclude that ICAM-1 expressed on the effector cytotoxic CD4+ T lymphocytes delivers regulatory signals that enhance IFN-gamma secretion.
Katsumoto
Y
Y
Department of Surgery II, Osaka University Medical School, Japan.
Monden
T
T
Takeda
T
T
Haba
A
A
Ito
Y
Y
Wakasugi
E
E
Wakasugi
T
T
Sekimoto
M
M
Kobayashi
T
T
Shiozaki
H
H
Shimano
T
T
Monden
M
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D002448:Cell Adhesion / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007167:Immunotherapy; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology; D009369:Neoplasms / Q000628:therapy; D010844:Picibanil / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology*; D013964:Thyroid Neoplasms / Q000276:immunology / Q000628:therapy; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D018799:Intercellular Adhesion Molecule-1; D010844:Picibanil