Interleukin-18, interferon-gamma, IP-10, and Mig expression in Epstein-Barr virus-induced infectious mononucleosis and posttransplant lymphoproliferative disease.
T cell immunodeficiency plays an important role in the pathogenesis of posttransplant lymphoproliferative disease (PTLD) by permitting the unbridled expansion of Epstein-Barr virus (EBV)-infected B lymphocytes. However, factors other than T cell function may contribute to PTLD pathogenesis because PTLD infrequently develops even in the context of severe T cell immunodeficiency, and athymic mice that are T-cell-immunodeficient can reject EBV-immortalized cells. Here we report that PTLD tissues express significantly lower levels of IL-18, interferon-gamma (IFN-gamma), Mig, and RANTES compared to lymphoid tissues diagnosed with acute EBV-induced infectious mononucleosis, as assessed by semiquantitative RT-PCR analysis. Other cytokines and chemokines are expressed at similar levels. Immunohistochemistry confirmed that PTLD tissues contain less IL-18 and Mig protein than tissues with infectious mononucleosis. IL-18, primarily a monocyte product, promotes the secretion of IFN-gamma, which stimulates Mig and RANTES expression. Both IL-18 and Mig display antitumor activity in mice involving inhibition of angiogenesis. These results document greater expression of IL-18, IFN-gamma, Mig, and RANTES in lymphoid tissues with acute EBV-induced infectious mononucleosis compared to tissues with PTLD and raise the possibility that these mediators participate in critical host responses to EBV infection.
Laboratory of Pathology,* Hematopathology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
J
J
Setsuda
J
J
Teruya-Feldstein
N L
NL
Harris
J A
JA
Ferry
L
L
Sorbara
G
G
Gupta
E S
ES
Jaffe
G
G
Tosato
D000293:Adolescent; D000328:Adult; D018946:Chemokine CCL5 / Q000378:metabolism; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007244:Infectious Mononucleosis / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18 / Q000378:metabolism*; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation; D011183:Postoperative Complications; D020133:Reverse Transcriptase Polymerase Chain Reaction
C080810:CXCL9 protein, human; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18