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1996-03-09
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Document 0134
DOCN M9650134
TI IL-12 expression in AIDS-related lymphoma B cell lines.
DT 9605
AU Benjamin D; Sharma V; Kubin M; Klein JL; Sartori A; Holliday J;
Trinchieri G; Division of Hematology and Oncology, Arthur G. James
Cancer; Hospital and Research Institute, Columbus, OH 43210, USA.
SO J Immunol. 1996 Feb 15;156(4):1626-37. Unique Identifier : AIDSLINE
MED/96164595
AB IL-12 is a 70-kDa heterodimer formed by the 40-kDa heavy chain (p40) and
the 35-kDa light chain (p35). Twenty-five Burkitt's lymphoma cell lines
(CL) and seven normal lymphoblastoid B CL were studied. The Burkitt's CL
included AIDS-associated B CL (AABCL) (7 EBV+/2 EBV-) and non-AABCL (8
EBV+/8 EBV-). Reverse transcription-PCR detected p40 in EBV+ AABCL (7 of
7), EBV+ non-AABCL (3 of 8), and normal lymphoblastoid B CL (6 of 6) but
not in EBV- CL (0 of 10). p35 mRNA was detected in 30 of 30 CL.
Constitutive secretion of p40 was found in 7 of 7 EBV+ AABCL (range,
341-18,086 pg/ml) and p70 in 3 of 7 EBV+ AABCL (range, 25-197 pg/ml),
but in only 1 of 8 EBV+ non-AABCL and 0 of 7 normal lymphoblastoid CL.
PMA stimulated p40 secretion in 7 of 7 EBV+ AABCL and p70 secretion in 5
of 7 EBV+ AABCL. PMA also triggered p40 and p70 secretion in 2 EBV+
non-AABCL and in 3 of 7 normal lymphoblastoid CL. No IL-12 secretion was
detected in 10 EBV- CL, including EBV- AABCL. The CL produced IL-10, a
known inhibitor of IL-12, but anti-IL-10 Abs did not neutralize IL-12.
Similarly, neutralizing anti-IFN gamma Abs or IFN gamma did not affect B
cell IL-12. For IL-12R studies, reverse transcription-PCR and 125I-IL-12
binding assays were performed. Although all CL tested showed mRNA
accumulation for one of the IL-12R components, IL-12 binding sites were
detected in only 1 of 30 CL. Our data suggest that: 1) AABCL
constitutively secrete large amounts of IL-12, contrasting with low
IL-12 production by HIV-1 infected PBMC; 2) lack of IL-12 expression in
EBV- AABCL suggests that in vivo exposure of B cells to HIV-1 only does
not induce IL-12 secretion and that both HIV-1 and EBV are required; 3)
the autocrine-negative effect of IL-10 on IL-12 in monocytes and the
enhancing effect of IFN gamma on IL-12 secretion do not apply to B cells
derived from AIDS patients.
DE Acquired Immunodeficiency Syndrome/COMPLICATIONS/*IMMUNOLOGY Base
Sequence Burkitt's Lymphoma/METABOLISM Cloning, Molecular DNA
Primers/CHEMISTRY Gene Expression Human Interferon Type II/METABOLISM
Interleukin-10/METABOLISM Interleukin-12/GENETICS/*METABOLISM
Lymphoma, B-Cell/COMPLICATIONS/*METABOLISM Molecular Sequence Data
Receptors, Interleukin/GENETICS/METABOLISM RNA, Messenger/GENETICS
Support, U.S. Gov't, P.H.S. Tumor Cells, Cultured JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).