CD4+ T cell-induced differentiation of EBV-transformed lymphoblastoid cells is associated with diminished recognition by EBV-specific CD8+ cytotoxic T cells.
EBV transformation of human B cells in vitro results in establishment of immortalized cell lines (lymphoblastoid cell lines (LCL)) that express viral transformation-associated latent genes and exhibit a fixed, lymphoblastoid phenotype. In this report, we show that CD4(+) T cells can modify the differentiation state of EBV-transformed LCL. Coculture of LCL with EBV-specific CD4(+) T cells resulted in an altered phenotype, characterized by elevated CD38 expression and decreased proliferation rate. Relative to control LCL, the cocultured LCL were markedly less susceptible to lysis by EBV-specific CD8(+) CTL. In contrast, CD4(+) T cell-induced differentiation of LCL did not diminish sensitivity of LCL to lysis by CD8(+) CTL specific for an exogenously loaded peptide Ag or lysis by alloreactive CD8(+) CTL, suggesting that differentiation is not associated with intrinsic resistance to CD8(+) T cell cytotoxicity and that evasion of lysis is confined to EBV-specific CTL responses. CD4(+) T cell-induced differentiation of LCL and concomitant resistance of LCL to lysis by EBV-specific CD8(+) CTL were associated with reduced expression of viral latent genes. Finally, transwell cocultures, in which direct LCL-CD4(+) T cell contact was prevented, indicated a major role for CD4(+) T cell cytokines in the differentiation of LCL.
Khanolkar
Aaruni
A
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Fu
Zheng
Z
Underwood
L Joey
LJ
Bondurant
Kristy L
KL
Rochford
Rosemary
R
Cannon
Martin J
MJ
D000328:Adult; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018968:CD58 Antigens / Q000096:biosynthesis / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002461:Cell Line, Transformed / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002472:Cell Transformation, Viral / Q000276:immunology*; D018920:Coculture Techniques; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006680:HLA Antigens / Q000096:biosynthesis; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006801:Humans; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D017735:Virus Latency / Q000235:genetics / Q000276:immunology
D018968:CD58 Antigens; D015815:Cell Adhesion Molecules; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger