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ILA, the human 4-1BB homologue, is inducible in lymphoid and other cell
lineages
H Schwarz, J Valbracht, J Tuckwell, J von Kempis and M Lotz
Sam and Rose Stein Institute for Research on Aging, San Diego, La Jolla,
CA.
We recently identified a gene that is induced by lymphocyte activation
(ILA). The sequence of the full-length 1.4-kb cDNA characterized ILA as a
new member of the nerve growth factor/tumor necrosis factor (NGF/TNF)
receptor family and the human homologue of the murine T-cell-specific
receptor 4-1BB. The present study demonstrates ILA mRNA isoforms at 4.4,
4.0, and 1.8 kb in poly-A+ RNA from activated, but not from resting human
peripheral blood T lymphocytes. A reverse transcriptase- polymerase chain
reaction (RT-PCR) assay was used to study tissue distribution and
regulation of ILA expression. The gene was induced in T lymphocytes by
phytohemagglutinin (PHA), phorbol myristate acetate (PMA), and antibody to
CD3, in B lymphocytes by PMA and antibodies to cell surface Ig, and in
blood monocytes by interleukin-1 beta (IL-1 beta), lipopolysaccharide
(LPS), and PMA. In T lymphocytes, ILA mRNA was detectable 1.5 hours after
stimulation, reached maximal levels at 8 hours, and declined to background
levels by 48 hours. Induction of ILA mRNA required protein synthesis and
was primarily due to increased transcription. Actinomycin D reduced ILA
mRNA levels in activated lymphocytes 50% within 30 minutes, demonstrating a
relatively short half-life of this mRNA. Analysis of nonlymphoid cells
showed that ILA mRNA was not detectable in resting cells. However, in
contrast to the lymphoid-specific expression of the murine 4-1BB gene, ILA
was detected in nonlymphoid cells, including epithelial and hepatoma cells
after stimulation with IL-1 beta. ILA was not detectable in several brain
derived cell lines. The ILA cDNA encodes a 30-kD protein as demonstrated by
in vitro translation, and this protein is immunoprecipitated by antisera
that were raised against ILA peptides or a glutathione-S-transferase fusion
protein. Flow cytometry showed expression of ILA protein on a subset of
activated T or B lymphocytes. In conclusion, activation-dependent
expression of ILA is found not only in T lymphocytes, but also in B
lymphocytes, monocytes, and diverse nonlymphoid cell types.
Volume 85,
Issue 4,
pp. 1043-1052,
02/15/1995
Copyright © 1995 by The American Society of Hematology
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