Characteristics of human EBV-specific cytotoxic T lymphocytes utilized for adoptive immunotherapy of EBV-induced lymphoproliferations in xenografted SCID mice

• Published in: Annals of oncology Vol. 8; no. suppl-2; pp. S137 - S140
• Main Authors: Lacerda, J. F., O'Reilly, R. J.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Oxford Oxford University Press 1997
• Subjects: AIDS/HIV; Animals; Antineoplastic agents; Biological and medical sciences; bone marrow transplantation; Bone Marrow Transplantation - immunology; Cell Division - immunology; Cell Division - radiation effects; cytotoxic T lymphocyte; Epstein-Barr virus; Herpesvirus 4, Human - isolation & purification; HLA Antigens - blood; Humans; Immunophenotyping; Immunotherapy; Immunotherapy, Adoptive; lymphoproliferative disorders; Lymphoproliferative Disorders - immunology; Lymphoproliferative Disorders - virology; Medical sciences; Mice; Mice, SCID; Pharmacology. Drug treatments; severe combined immune dificiency mice; Severe Combined Immunodeficiency - virology; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - radiation effects; T-Lymphocytes, Cytotoxic - virology; Transplantation, Heterologous; Gammaherpesvirinae; Herpesviridae; Rodentia; Cytotoxicity; Malignant hemopathy; Autologous system; Epstein Barr virus; In vitro; Lymphoma; Mechanism; Adoptive transfer; Virus; In vivo; Vertebrata; Experimental disease; Specificity; Mammalia; Treatment; Histocompatibility restriction; Mouse; Lymphoproliferative syndrome; Animal; Immunotherapy; T-Lymphocyte
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/8.suppl_2.S137

Human Epstein-Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs) prolong the survival of mice with severe combined immune deficiency bearing the autologous, but not HLA-mis-matched, human EBV-induced lymphoproliferative disorders (EBV-LPDs). In the present study, we demonstrate that the HLA-restricted activity displayed by EBV-CTLs both in vitro and in vivo correlates with their in vivo homing pattern, and further characterize these effectors. EBV-CTLs were CD3+, CD16/56-, TCR α/β+, predominantly CD8+ and CD4−, and had a high expression of T-cell activation antigens. EBV-CTLs were positive for CD11a/CD18, CD54, CD58, CD44, CD49d, CD28, and CD45RO, and negative for CD45RA, CD11b, CD11c. After 26 days in culture, EBV-CTLs displayed strong cytotoxicity against the autologous EBV-transformed B-cell line (EBV-LCL), which was inhibited by the addition of anti-CD3 MoAb and mostly HLA class I-restricted. Unirradiated and irradiated EBV-CTLs in the absence of IL-2 failed to proliferate after more than 2 days in culture with the autologous EBV-LCLs, while unirradiated EBV-CTLs with IL-2 formed large colonies and had a high thymidine incorporation both on days 5 and 8. The cytotoxicity of irradiated EBV-CTLs against the autologous EBV-LCLs was conserved. It remains to be determined whether irradiated EBV-CTLs are capable of homing to EBV-LPDs in vivo and to mediate a therapeutic response comparable to that observed with unirradiated EBV-CTLs.