title: Differential chemokine, chemokine receptor and cytokine expression in Epstein-Barr virus-associated lymphoproliferative diseases.
abstract: T cell immunity plays an important role in the clinicopathology of Epstein-Barr virus (EBV)-associated diseases. Acute EBV-induced infectious mononucleosis (IM) is a common self-limiting disease, however, other EBV-associated diseases, including chronic active EBV infection (CAEBV), NK cell lymphoma (NKL), and Hodgkin's lymphoma (HL), exhibit distinct clinical features. Chemokines are members of a family of small-secreted proteins. The relationships between chemokines and the chemokine receptor (R) are thought to be important for selectivity of local immunity. Some chemokines, chemokine R and cytokines closely associate with the T cell subtypes, Th1 and Th2 T cells and cytotoxic cells. To clarify the role of T cell immunity in EBV-associated diseases, we conducted gene expression profiling, using chemokine, chemokine R and cytokine DNA chips. Compared to EBV negative non-specific lymphadenitis, CAEBV and NKL exhibited diffuse down- and up-regulation, respectively, of these gene profiles. IM had a predominantly Th1-type profile, whereas HL had a mixed Th1/Th2-type profile. Reduction of the Th1-type cytokine interferon gamma (IFN-gamma) in CAEBV was confirmed by Reverse transcriptase-polymerase chain reaction, whereas IFN-gamma expression was markedly enhanced in NKL, and moderately enhanced in IM. Compared to IM, CAEBV showed slight elevation of "regulated upon activation, normal T expressed and secreted" (RANTES), but almost all other genes assayed were down-regulated. NKL exhibited elevated expression of numerous genes, particularly IFN-gamma-inducible-10 (IP-10) and monokine induced by IFN-gamma (MIG). HL showed variable elevated and reduced expression of various genes, with increased expression of IL-13 receptor and MIG. Our study demonstrated the enormous potential of gene expression profiling for clarifying the pathogenesis of EBV-associated diseases.
authors.affiliation: Department of Pathology, School of Medicine, Fukuoka University, Nanakuma 7-45-1, Jonan-ku, Fukuoka 814-01, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohshima
authors.forename: Kennosuke
authors.initials: K
authors.lastname: Karube
authors.forename: Makoto
authors.initials: M
authors.lastname: Hamasaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tutiya
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Suefuji
authors.forename: Keiko
authors.initials: K
authors.lastname: Suzuki
authors.forename: Junji
authors.initials: J
authors.lastname: Suzumiya
authors.forename: Shouichi
authors.initials: S
authors.lastname: Ohga
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kikuchi
mesh_terms: D000293:Adolescent; D000328:Adult; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D004854:Herpesvirus 4, Human; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D008199:Lymphadenitis / Q000276:immunology / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D018925:Chemokines; D016207:Cytokines; D012333:RNA, Messenger; D019707:Receptors, Chemokine