Upregulation of B7 molecules by the Epstein-Barr virus enhances susceptibility to lysis by a human NK-like cell line.
The original human NK-like line YT was reported to lyse K562 and several B- and T-cell lines. The YT subline we are investigating, YT-INDY, does not lyse K562 or the T-cell line Molt-4. It does, however, lyse the EBV+ Burkitt lymphoma (BL) B-cell line Raji and EBV-immortalized B-cell lines. Several EBV- BL lines and an EBV- pre-B-cell leukemia line that we tested were not appreciably lysed by YT-INDY. To determine if EBV plays a role in TC susceptibility to lysis by YT-INDY, we compared YT-INDY's ability to lyse the EBV- BL line BL41 to its ability to lyse an EBV-infected derivative of BL41. The EBV-infected cell line was lysed, on average, at twice the level of the uninfected line. CD28/B7 interactions appeared to be involved in TC recognition by YT-INDY. Therefore, we examined the level of expression of B7 molecules on the infected and uninfected BL41 lines. An average of 15% of the uninfected BL41 cells expressed B7-1/B7-3, compared to 79% of the infected. B7-2 expression was similar in the two cell lines. Lysis of EBV-infected BL41 was reduced by anti-B7-1/B7-3 (BB1) or anti-CD28 antibodies (Abs) to the level of lysis of the uninfected line, indicating that upregulation of B7-1/B7-3 by the virus may be responsible for the enhanced susceptibility. We attempted to determine the particular EBV latent protein responsible for B7-1/B7-3 upregulation by analyzing BL41 clones expressing LMP1, EBNA-2/EBNA-LP, or EBNA-1. All of the high-expressing clones showed a higher level of B7-1/B7-3 expression than the vector-transfected control cell line, with LMP1-expressing clones expressing the highest amount. EBNA-1 clones and a high-expressing EBNA-2/EBNA-LP clone had a slightly higher density of B7-2 on their surface than the remaining clones. The increased expression of molecules of the B7 family correlated with increased susceptibility of the clones to lysis by YT-INDY. Anti-CD28 or a combination of anti-B7-1/B7-3 and anti-By-2 did not inhibit lysis of the clones to the level of lysis of the vector-transfected control cell line in all cases. We conclude that intact EBV enhances susceptibility to YT-INDY lysis by upregulating B7-1/B7-3. EBV proteins expressed individually also enhance susceptibility to lysis and upregulate members of the B7 family.(ABSTRACT TRUNCATED AT 400 WORDS)
Montel
A H
AH
Department of Microbiology/Immunology, Indiana University School of Medicine, Indianapolis 46202-5200.
Morse
P A
PA
Brahmi
Z
Z
D001402:B-Lymphocytes / Q000276:immunology; D018122:B7-1 Antigen / Q000096:biosynthesis*; D018106:CD28 Antigens / Q000096:biosynthesis*; D015815:Cell Adhesion Molecules / Q000276:immunology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000502:physiology*; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology*; D008934:Mitogens / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology
D018122:B7-1 Antigen; D018106:CD28 Antigens; D015815:Cell Adhesion Molecules; D008934:Mitogens; D014764:Viral Proteins