| Abstract: |
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-mismatched, 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. |
| Keywords: |
controlled study; human cell; nonhuman; conference paper; cd3 antigen; cd8 antigen; animal cell; mouse; animals; mice; cell division; interleukin 2; animal model; cytotoxicity; mice, scid; monoclonal antibody; t lymphocyte receptor; cd16 antigen; immunotherapy; xenograft; cd11b antigen; hla antigen class 2; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; hla antigen class 1; transplantation, heterologous; immunophenotyping; lymphoproliferative disease; cd4 antigen; hermes antigen; bone marrow transplantation; severe combined immunodeficiency; intercellular adhesion molecule 1; lymphocyte function associated antigen 3; adoptive immunotherapy; immunotherapy, adoptive; hla antigen; hla antigens; scid mouse; epstein barr virus; cd28 antigen; cd45 antigen; thymidine; herpesvirus 4, human; lymphoproliferative disorders; cd56 antigen; lymphocyte function associated antigen 1; glycoprotein p 15095; epstein-barr virus; cd18 antigen; humans; human; priority journal; cytotoxic t lymphocytes; severe combined immune deficiency mice
|
