Local suppression of Epstein-Barr virus (EBV)-specific cytotoxicity in biopsies of EBV-positive Hodgkin's disease.
Epstein-Barr virus (EBV)-positive Hodgkin's and Reed-Sternberg (HRS) cells express the virus-encoded latent membrane proteins LMP1 and LMP2 that could serve as rejection targets in Hodgkin's disease (HD). To examine whether EBV-triggered reactivities can be detected in the tumor, we have compared cytokine mRNA expression, cell phenotype, and cytotoxic activity in biopsies from 8 EBV-carrying and 6 EBV-HD patients. Neither the pattern of lymphokine production nor the cell phenotype of the in vivo-activated interleukin-2-responding populations provided a clear discrimination between EBV+ and EBV- cases. HLA class I-restricted EBV-specific cytotoxicity was shown in interleukin-2-dependent cultures from 3 of 3 EBV- tumors, whereas cultures from 6 of 6 EBV+ tumors were either noncytotoxic or exerted LAK-type cytotoxicity. EBV-specific cytotoxic T lymphocyte precursors were present in the blood of 1 patient carrying an EBV+ tumor. The results suggest that a tumor-associated suppression of EBV-specific T-cell responses may play an important role in the pathogenesis of EBV+ HD.
Frisan
T
T
Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
Sjöberg
J
J
Dolcetti
R
R
Boiocchi
M
M
De Re
V
V
Carbone
A
A
Brautbar
C
C
Battat
S
S
Biberfeld
P
P
Eckman
M
M
D000328:Adult; D000368:Aged; D001483:Base Sequence; D016207:Cytokines / Q000235:genetics; D003602:Cytotoxicity, Immunologic; D017931:DNA Primers / Q000737:chemistry; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006689:Hodgkin Disease / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D007108:Immune Tolerance; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D016207:Cytokines; D017931:DNA Primers; D004279:DNA, Viral; D012333:RNA, Messenger; D012334:RNA, Neoplasm