Antigen presenting phenotype of Hodgkin Reed-Sternberg cells: analysis of the HLA class I processing pathway and the effects of interleukin-10 on epstein-barr virus-specific cytotoxic T-cell recognition.
Approximately 40% of Hodgkin's disease (HD) cases in Western countries carry Epstein-Barr virus (EBV) in the malignant Hodgkin-Reed-Sternberg (H-RS) cells. HLA class I-restricted cytotoxic T lymphocytes (CTLs) with specificity for viral antigens expressed in H-RS cells therefore have therapeutic potential. However, a prerequisite for CTL therapy is that the tumor target be capable of processing and presenting endogenously expressed antigens via the transporter associated with antigen processing (TAP)-dependent HLA class I pathway. We have assessed the antigen-presenting phenotype of H-RS cells in two ways. First, immunohistochemical analysis of 38 HD biopsies showed that H-RS cells were uniformly TAP1/TAP2-positive and expressed HLA class I in the majority (18 of 24, 75%) of EBV-positive cases compared with only 4 of 14 (29%) of EBV-negative cases. Second, using a panel of 5 H-RS cell lines, we showed that 4 of 5 could process and present EBV proteins to HLA class I-restricted EBV-specific CTL clones. Others have reported that human interleukin-10 (IL-10), which is expressed by H-RS cells in the majority of EBV-positive HD cases, can abrogate CTL recognition in some circumstances. However, IL-10 pretreatment of the H-RS lines or of the EBV-specific CTLs had no such effect in this system. These results support the possibility that EBV-specific CTLs may be used to treat virus-positive HD.
CRC Institute for Cancer Studies, University of Birmingham, Birmingham, UK. s.p.lee@bham.ac.uk
S P
SP
Lee
C M
CM
Constandinou
W A
WA
Thomas
D
D
Croom-Carter
N W
NW
Blake
P G
PG
Murray
J
J
Crocker
A B
AB
Rickinson
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000276:immunology*; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000145:classification / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology; D001706:Biopsy; D000939:Epitopes / Q000276:immunology; D006566:Herpesviridae Infections / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology* / Q000302:isolation & purification; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006689:Hodgkin Disease / Q000473:pathology* / Q000628:therapy / Q000821:virology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007167:Immunotherapy; D016753:Interleukin-10 / Q000494:pharmacology*; D010641:Phenotype; D016539:Reed-Sternberg Cells / Q000276:immunology* / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000956:Antigens, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; C073119:TAP1 protein, human; D014763:Viral Matrix Proteins; D016753:Interleukin-10; C071692:TAP2 protein, human