Basis for nonresponse: donor-derived EBV-specific T cells that failed to induce a clinical response did not exhibit cytotoxic activity against the spontaneously transformed EBV-BLCLs generated from the patient's tissues. (A) Cytotoxicity of donor EBV–specific CTLs. There were 8 responders (closed symbols) and 3 nonresponders (open symbols; n = 11) sensitized with autologous B95.8-transformed B cells against EBV B95.8–transformed donor–derived autologous BLCL and against donor-type spontaneous EBV-transformed BLCLs cultured from the patient blood or EBV-LPD. The B95.8-sensitized EBV-specific CTLs used in nonresponding patients lysed EBV B95.8 transformed BLCL but did not lyse the spontaneous EBV transformants of donor origin cultured from the patient. (B) Cytotoxicity of donor-derived EBV-CTLs stimulated with spontaneously transformed EBV-BLCLs of donor origin cultured from the patient. The same T cells as in panel A were stimulated in vitro with the spontaneously transformed EBV-BLCLs and were able to kill both the stimulating B-cell line and the donor-derived B95.8 transformant. These data confirm that the EBV-LPD is sensitive to lysis by donor-derived EBV-CTLs if the T cells are sensitized with the endogenous strain of EBV. (C) HLA restriction of EBV-CTLs generated from an HLA haplotype–matched donor for patient 13, who developed an EBV lymphoma in cord blood–derived B cells; these EBV-CTLs were selectively restricted by an HLA DRB, 0401, not shared by the cord blood cells and did not lyse cord blood donor-derived spontaneous EBV-BLCL generated from the tumor.