CD95 (Fas) ligand expression of Epstein-Barr virus (EBV)-infected lymphocytes: a possible mechanism of immune evasion in chronic active EBV infection.
The Epstein-Barr virus (EBV) induces infectious mononucleosis (IM) and can be associated with chronic active EBV infection (CAEBV). Cytotoxic T lymphocytes (CTL) play an important role in excluding EBV-infected cells. Two cytotoxic mechanisms of CTL have been demonstrated: one perforin/granzyme-based and the other Fas (CD95)/Fas ligand (FasL)-based. To clarify these two pathways in CAEBV, we analyzed six patients with CAEBV and four patients with IM using immunohistochemical staining of the lymph nodes. In both CAEBV and IM, CD8+ T-cells increased in number, but CD56+ natural killer cells were rare. In four of six cases with CAEBV, approximately half the lymphocytes were positive for T cell-restricted intracellular antigens (TIA-1), which were recognized by the cytolytic granules of CTL. In IM, the number of TIA-1 positive cells was smaller than that in CAEBV. Fas-positive lymphocytes were frequently encountered in both CAEBV and IM. However, FasL-positive lymphocytes increased in three of six patients with CAEBV, but not in patients with IM. Except for one case with CAEBV, the number of perforin- and/or granzyme-positive cells was small in number in both CAEBV and IM cases. In double-staining FasL and EBV in situ hybridization, FasL-positive EBV-infected lymphocytes were detected in CAEBV but not in IM. In CAEBV, the Fas/FasL pathway and not perforin pathways appears to play an important role in the pathogenesis. The data suggest that EBV-infected lymphocytes may evade immune attack through the expression of FasL.
Ohshima
K
K
Department of Pathology, School of Medicine, Fukuoka University, Japan.
Suzumiya
J
J
Sugihara
M
M
Nagafuchi
S
S
Ohga
S
S
Kikuchi
M
M
D000293:Adolescent; D000328:Adult; D019002:CD56 Antigen / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002648:Child; D002675:Child, Preschool; D053222:Fas Ligand Protein; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000254:growth & development; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007223:Infant; D007244:Infectious Mononucleosis / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D007694:Killer Cells, Natural / Q000166:cytology; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000737:chemistry* / Q000166:cytology / Q000821:virology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000096:biosynthesis; D008565:Membrane Proteins / Q000032:analysis; D054353:Perforin; D039102:Poly(A)-Binding Proteins; D052899:Pore Forming Cytotoxic Proteins; D011506:Proteins; D012367:RNA, Viral / Q000235:genetics; D016601:RNA-Binding Proteins / Q000032:analysis; D000074019:T-Cell Intracellular Antigen-1; D019014:fas Receptor / Q000032:analysis
D019002:CD56 Antigen; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D039102:Poly(A)-Binding Proteins; D052899:Pore Forming Cytotoxic Proteins; D011506:Proteins; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; D019014:fas Receptor; D054353:Perforin