Activation of interleukin-13 expression in T cells from HTLV-1-infected individuals and in chronically infected cell lines.
Human T-cell leukemia virus type 1 (HTLV-1) infection profoundly alters T-cell gene expression, and the dysregulated synthesis of cytokines could influence the course and pathologic consequences of infection. In the process of screening T-cell lines for T helper 1 (Th1) and Th2 cytokine mRNAs, we observed that interleukin-13 (IL-13) mRNA was highly expressed in HTLV-1-infected, IL-2-dependent T-cell lines. IL-9 and interferon gamma (IFN-gamma) mRNAs were also expressed at high levels in chronically infected cell lines. IL-5 mRNA was detected in 60% of the HTLV-1-infected cell lines, but mRNAs for IL-4, IL-10, IL-2, and IL-15 were either below detection limits or did not correlate with HTLV-1 infection. Transcriptional activation of the IL-13 promoter by the HTLV-1 Tax trans-regulatory protein was demonstrated in Jurkat T cells transiently transfected with an IL-13 promoter-reporter plasmid. The clinical relevance of these observations was demonstrated by immunofluorescent staining and flow cytometry of lymphocytes obtained from HTLV-1-infected patients. These studies revealed that IL-13 production was directly related to the level of Tax expression in the infected CD4+ T cells soon after in vitro culture. As IL-13 plays key roles in tumor immunosurveillance, asthma, and central nervous system inflammation, it may contribute to the pathophysiology of HTLV-1-associated diseases.
Chung
Hye-Kyung
HK
Basic Research Laboratory, Center for Cancer Research, NCI-Frederick, Frederick, MD 21702-1201, USA.
Young
Howard A
HA
Goon
Peter K C
PK
Heidecker
Gisela
G
Princler
Gerald L
GL
Shimozato
Osamu
O
Taylor
Graham P
GP
Bangham
Charles R M
CR
Derse
David
D
D016022:Case-Control Studies; D002461:Cell Line, Transformed; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D016356:Gene Products, tax / Q000235:genetics / Q000502:physiology; D015490:HTLV-I Infections / Q000473:pathology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D018793:Interleukin-13 / Q000096:biosynthesis* / Q000235:genetics; D015848:Interleukin-5 / Q000096:biosynthesis / Q000235:genetics; D016906:Interleukin-9 / Q000096:biosynthesis / Q000235:genetics; D019169:Jurkat Cells; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D015533:Transcriptional Activation; D014161:Transduction, Genetic
D016207:Cytokines; D016356:Gene Products, tax; D018793:Interleukin-13; D015848:Interleukin-5; D016906:Interleukin-9; D012333:RNA, Messenger; D007371:Interferon-gamma