CD30 signals integrate expression of cytotoxic effector molecules, lymphocyte trafficking signals, and signals for proliferation and apoptosis

H. Muta, L. H. Boise, L. Fang, E. R. Podack

Research output: Contribution to journalArticle

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Abstract

Although CD30 has long been recognized as an important marker on many lymphomas of diverse origin and as activation molecule on B cells and T cells, its primary function has remained obscure. We now report that CD30 signals may serve to inhibit effector cell activity by integrating gene expression changes of several pathways important for cytotoxlc NK and T cell effector function. In the large granular lymphoma line YT, CD30 signals down-regulate the expression of cytotoxic effector molecules, Fas ligand, perforin, granzyme B, and abrogate cytotoxicity, c-myc, a regulator of proliferation and an upstream regulator of Fas ligand expression, is completely suppressed by CD30. Furthermore, CD30 signals strongly induce CCR7, suggesting a role for CD30 signals in the homing of lymphocytes to lymph nodes. The up-regulation of Fas, death receptor 3, and TNF-related apoptosis-inducing ligand by CD30 indicates an increase in susceptibility to apoptotic signals whereas up-regulation of TNFR-associated factor 1 and cellular inhibitor of apoptosis 2 protect cells from certain types of apoptosis. Using gene microarrays, 750 gene products were induced and 90 gene products were suppressed >2-fold by CD30 signals. Signals emanating from CD30 use both TNFR-associated factor 2-dependent and -independent pathways. The integration of CD30 signals in a lymphoma line suggests that CD30 can down-modulate lymphocyte effector function and proliferation while directing the cells to lymph nodes and increasing their susceptibility to certain apoptotic signals. These studies may provide a molecular mechanism for the recently observed CD30-mediated suppression of CTL activity in vivo in a diabetes model.

Original languageEnglish
Pages (from-to)5105-5111
Number of pages7
JournalJournal of Immunology
Volume165
Issue number9
StatePublished - Nov 1 2000

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Lymphoma
Fas Ligand Protein
Apoptosis
Receptors, Tumor Necrosis Factor, Member 25
Up-Regulation
Lymph Nodes
TNF-Related Apoptosis-Inducing Ligand
Lymphocytes
Genes
CD95 Antigens
T-Lymphocytes
Natural Killer Cells
B-Lymphocytes
Down-Regulation
Gene Expression
lymphocyte effector molecules
perforin-granzyme B

ASJC Scopus subject areas

  • Immunology

Cite this

CD30 signals integrate expression of cytotoxic effector molecules, lymphocyte trafficking signals, and signals for proliferation and apoptosis. / Muta, H.; Boise, L. H.; Fang, L.; Podack, E. R.

In: Journal of Immunology, Vol. 165, No. 9, 01.11.2000, p. 5105-5111.

Research output: Contribution to journalArticle

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