Generation of memory CD4+, CD8+, CD45RO+ and CD16- lymphocytes activated with IL-2, INF-gamma, and TNF-alpha with specific cytotoxicity against autologous cervical cancer cells in a mixed leukocyte-tumour cell culture.
Cytotoxic T lymphocytes (CTL) specific against autologous human cervical cancer cells were generated in vitro from peripheral blood leukocytes (PBL) from four patients with non-keratinized epidermoid carcinoma. For this purpose, these patients' PBL were co-cultured for 28 days either with IL-2 or a mixture of IL-2, IFN-gamma and TNF-alpha in the presence of autologous tumour cells (ATC). Our results showed that these CTL were highly cytotoxic for ATC, weakly cytotoxic for heterologous cervical cancer tumour cells, and not cytotoxic for carcinoma cell lines, normal cervix cells nor autologous PBL. Proliferation and cytotoxicity against ATC were greater when the PBL were activated with the three cytokines. These CTL had a CD4:CD8 ratio of 1:1, were CD16- and CD45RO+ and their killing activity was inhibited by antibodies against CD3, CD8 and MHC-class I but not by antibodies against CD4, CD16 or HLA-class II. The possibility of generating specific CTL in long term cultures for cervical cancer therapy is also discussed.
Rangel
R
R
Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autonoma de Mexico, Mexico D.F.
Rocha
L
L
Ramirez
J L
JL
Ibarra
M J
MJ
Solorza
G
G
Monroy
A
A
Ramirez
M A
MA
Herrera
A
A
Weiss-Steider
B
B
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015551:Autoimmunity; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology; D002584:Cervix Uteri / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D006680:HLA Antigens / Q000032:analysis / Q000276:immunology; D006681:HLA-D Antigens / Q000032:analysis / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects*; D007371:Interferon-gamma / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D007822:Laryngeal Neoplasms / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D007959:Lymphocyte Culture Test, Mixed; D016131:Lymphocyte Subsets / Q000737:chemistry / Q000187:drug effects*; D016853:Muromonab-CD3 / Q000494:pharmacology; D017452:Receptors, IgG / Q000032:analysis / Q000276:immunology; D011994:Recombinant Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000473:pathology
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens; D006680:HLA Antigens; D006681:HLA-D Antigens; D007376:Interleukin-2; D016853:Muromonab-CD3; D017452:Receptors, IgG; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens