AACR: CD30, CD153 Expression on Normal, Malignant Cells

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AACR Abstract Number: 4672

CD30 function on normal human T cells

Kenichi Ito and Eckhard R. Podack. Department of Microbiology and

Immunology, University of Miami School of Medicine, Miami, FL.

Background: CD30, a member of the TNF-receptor family, is expressed

on many types of Lymphomas, germ cell tumors and multiple myeloma.

Its ligand, CD30-L (CD153), a member of the TNF family, is expressed

in chronic lymphocytic leukemia, follicular B cell lymphoma, T-cell

lymphoblastic lymphoma, and adult T cell leukemia/lymphoma. CD30 may

control apoptosis, cell activation, effector function, and

proliferation.

Despite its important clinical role, CD30 function is not well

understood. The reason probably lies in a lack of good tools for

analyzing CD30. In order to analyze human CD30 function in detail, we

have tried to use human T cells. However, under unstimulated

condition, few cells express CD30 in normal human T cells. We now

report that CD45RO+ T (memory) cells when stimulated with OKT3

express high levels of CD30+ cells. Using CD45RO+ cells the

functional role of CD30 is studied.

Methods and Results: Normal human T cells from healthy volunteers

were used to purify CD45RO+ T cells by magnetic sorting, at this

stage they are CD30 negative. After stimulation with OKT3, anti-CD28,

and IL-15 or IL-2, 40% of the cells expressed CD30. CD30+ and CD30-

cells were separated by cell sorting or magnetic sorting and compared

by phenotype and function. Phenotypically CD30+ cells expressed

higher levels of CCR7, CD30-L, CD40, and CD40-L when compared to CD30-

cells. When stimulated with the anti-CD30 agonistic antibody C10 and

OKT3, CD30+ cells produced significantly more IL-5, IL-13, and IFN-ã

compared to CD30- cells. There was no IL-4 production and no

difference in IL-10. Regarding cytotoxicity activity, both CD30+ and

CD30- cells had similar cytotoxic activity. We also found that CD30

expression was dynamic. After CD30 sorting, we re-stimulated CD30-

cells with OKT3 and IL-15, and observed that a significant number of

previously negative cells became CD30+.

Comparison of gene expression patterns between the CD30+ YT lymphoma

cell line and normal human T cells using cDNA microarray analysis

will highlight changes in CD30 signaling that may be specific to

lymphoma cells and may contribute to oncogenic transformation.

Presenter: Kenichi Ito

Affiliation: Department of Microbiology and Immunology, University of

Miami School of Medicine, Miami, FL; E-mail: haruharumito@...

Copyright © 2004 American Association for Cancer Research. All rights

reserved. Citation information: Proceedings of the AACR, Volume 45,

March 2004.