Defective immune function of primary effusion lymphoma cells is associated with distinct KSHV gene expression profiles.
Primary effusion lymphomas (PEL) are uniformly infected with Kaposi's sarcoma-associated herpesvirus (KSHV), and thus likely present both tumor and viral antigens to the immune system. In order to grow unrestricted and cause disease, multiple immune evasion strategies may be utilized by PEL to evade immune surveillance. Using six well-established PEL cell lines and comparing these to Epstein-Barr virus-transformed B cell lines and peripheral blood B cells, significant differences were found in the surface expression of molecules involved in antigen presentation, T cell activation and cell-cell adhesion. Significantly reduced stimulation of cytotoxic T lymphocytes, lowered sensitivity to natural killer cell-mediated lysis and impaired function as antigen presenting cells in mixed leukocyte reactions were found for three PEL cell lines with particularly low CD54, CD58 and CD81 expression. Comparative microarray analysis demonstrated specific patterns of KSHV-encoded gene expression that were associated with the different immune functions of these cell lines. Thus, the present data suggest that distinct patterns of KSHV gene expression may be associated with particular phenotypic and functional characteristics of PEL cells, which may influence PEL pathogenesis.
Suscovich
Todd J
TJ
Partners AIDS Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
Paulose-Murphy
Mini
M
Harlow
Jason D
JD
Chen
Yidong
Y
Thomas
Seddon Y
SY
Mellott
Tiffany J
TJ
Walker
Bruce D
BD
Scadden
David T
DT
Zeichner
Steven
S
Brander
Christian
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017951:Antigen Presentation / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D002448:Cell Adhesion; D004273:DNA, Neoplasm / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis; D020869:Gene Expression Profiling; D005814:Genes, Viral / Q000502:physiology*; D019288:Herpesvirus 8, Human / Q000235:genetics*; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D004273:DNA, Neoplasm; D004279:DNA, Viral